Exploration of Immunology

Open Access

Review

Vitamin D and immunomodulation in the skin: a useful affirmative nexus

Skin is the largest organ of the body having multifunctional activities. It has a dynamic cellular network with unique immunologic properties to maintain defensive actions, photoprotection, immune r [...] Read more.

Saptadip Samanta

Published: June 30, 2021 Explor Immunol. 2021;1:90–111
DOI: https://doi.org/10.37349/ei.2021.00009
This article belongs to the special issue Cross Talk Among Skin Cells and Immune Cells

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Open Access

Review

Interplay between mesenchymal stromal cells and immune system: clinical applications in immune-related diseases

Mesenchymal stromal cells (MSCs) are a mesodermal stem cell population, with known self-renewal and multilineage differentiation properties. In the last century, MSCs have been widely used in regene [...] Read more.

Panagiotis Mallis ... Catherine Stavropoulos Giokas

Published: June 30, 2021 Explor Immunol. 2021;1:112–139
DOI: https://doi.org/10.37349/ei.2021.00010

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Open Access

Review

Severe acute respiratory syndrome coronavirus 2 targeted antibodies cocktail and B cell receptor interplay: interventions to trigger vaccine development

Coronavirus disease-2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV)-2 spread globally and creates an alarming situation. Following the SARS-CoV-2 paradigm, therape [...] Read more.

Kabeer Haneef ... Zainab Fatima

Published: August 31, 2021 Explor Immunol. 2021;1:140–154
DOI: https://doi.org/10.37349/ei.2021.00011
This article belongs to the special issue Vaccine-induced Immune Responses Against SARS-CoV-2 Infections

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Open Access

Review

Immunosuppressive microenvironment in oral cancer: implications for cancer immunotherapy

Head and neck squamous cell carcinoma (HNSCC) is a relatively widespread cancer with high mortality rates. Many patients with locally advanced disease are treated with combinations of surgery, radia [...] Read more.

Shalini K. Sureshbabu ... Shubhada V. Chiplunkar

Published: August 31, 2021 Explor Immunol. 2021;1:166–198
DOI: https://doi.org/10.37349/ei.2021.00013

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Open Access

Original Article

Conserved envelope protein of nCoV2 as the possible target to design polytope vaccine

Aim: The envelope protein of novel coronavirus 2 (nCoV2) was reported to be highly conserved compared to its spike (S) protein which was shown to undergo several alterations in their amino acid seq [...] Read more.

Aim: The envelope protein of novel coronavirus 2 (nCoV2) was reported to be highly conserved compared to its spike (S) protein which was shown to undergo several alterations in their amino acid sequences in the span of one year (2020–2021). Therefore, it is aimed to consider highly conserved structural protein of nCov2 namely envelope (E) protein to design the polytope for the formulation of the vaccine against coronavirus disease 2019 (Covid-19). Methods: Online in silico tools were employed to decipher the conservancy and antigenicity of E-protein of nCoV2. They are: to evaluate the molecular affinities among the chosen representatives of alpha and beta coronaviruses, the Molecular Evolutionary Genetics Analysis (MEGA) X 10.1.1 was used. Immune Epitope Database (IEDB)-NetMHCpan (ver. 4.1) tool was used to predict the epitopes of E protein binding to the frequently distributed major histocompatibility complex (MHC) I alleles. ProtParam, VaxJen, ToxinPred and AllerTop online tools were used to assess the physicochemical features, antigenicity, non-toxin and non-allergen aspects of constructed polytope. Secondary structure analysis and homology modelling validation of polytope were done using Phyre2 online tool. Discontinuous and linear epitopes of the designed polytope were predicted through IEDB Ellipro tool. Population coverage of epitopes of the polytope was performed using IEDB online tool with the frequent distribution of human leukocyte antigen (HLA) I alleles in the South Indian Asian population. Results: The phylogeny of envelope proteins of chosen representatives of Coronaviridae confirmed its conservancy and possible origin of nCoV2 from alpha coronaviruses through vampire CoV2. The designed polytope of E-protein was with 53 amino acid residues. The same was developed by linking with cysteine and serine (CS) residues in between epitopes. Conclusion: The antigenicity, non-allergen, non-toxin, homology modelling, discontinuous and linear epitopes of the designed polytope authenticate to explore the envelope protein for prophylactic measures. The epitopes of polytope were found to restrict to MHC I alleles occurring frequently among South Indian Asians.

Krupanidhi Sreerama

Published: August 31, 2021 Explor Immunol. 2021;1:155–165
DOI: https://doi.org/10.37349/ei.2021.00012
This article belongs to the special issue Vaccine-induced Immune Responses Against SARS-CoV-2 Infections

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Aim: The envelope protein of novel coronavirus 2 (nCoV2) was reported to be highly conserved compared to its spike (S) protein which was shown to undergo several alterations in their amino acid sequences in the span of one year (2020–2021). Therefore, it is aimed to consider highly conserved structural protein of nCov2 namely envelope (E) protein to design the polytope for the formulation of the vaccine against coronavirus disease 2019 (Covid-19). Methods: Online in silico tools were employed to decipher the conservancy and antigenicity of E-protein of nCoV2. They are: to evaluate the molecular affinities among the chosen representatives of alpha and beta coronaviruses, the Molecular Evolutionary Genetics Analysis (MEGA) X 10.1.1 was used. Immune Epitope Database (IEDB)-NetMHCpan (ver. 4.1) tool was used to predict the epitopes of E protein binding to the frequently distributed major histocompatibility complex (MHC) I alleles. ProtParam, VaxJen, ToxinPred and AllerTop online tools were used to assess the physicochemical features, antigenicity, non-toxin and non-allergen aspects of constructed polytope. Secondary structure analysis and homology modelling validation of polytope were done using Phyre2 online tool. Discontinuous and linear epitopes of the designed polytope were predicted through IEDB Ellipro tool. Population coverage of epitopes of the polytope was performed using IEDB online tool with the frequent distribution of human leukocyte antigen (HLA) I alleles in the South Indian Asian population. Results: The phylogeny of envelope proteins of chosen representatives of Coronaviridae confirmed its conservancy and possible origin of nCoV2 from alpha coronaviruses through vampire CoV2. The designed polytope of E-protein was with 53 amino acid residues. The same was developed by linking with cysteine and serine (CS) residues in between epitopes. Conclusion: The antigenicity, non-allergen, non-toxin, homology modelling, discontinuous and linear epitopes of the designed polytope authenticate to explore the envelope protein for prophylactic measures. The epitopes of polytope were found to restrict to MHC I alleles occurring frequently among South Indian Asians.

Open Access

Review

Macrophages and fibroblasts underpin skin immune responses

There are various types of skin immune responses including inflammatory skin diseases and skin malignancy. Macrophages and fibroblasts are skin resident cells that had been overlooked in terms of im [...] Read more.

There are various types of skin immune responses including inflammatory skin diseases and skin malignancy. Macrophages and fibroblasts are skin resident cells that had been overlooked in terms of immunological research targets. In this review, cross talk among macrophages, fibroblasts, and migratory immune cells in skin diseases such as atopic dermatitis (AD), contact hypersensitivity, psoriasis, systemic sclerosis, melanoma, and cutaneous T-cell lymphoma is described. Macrophages are important in AD by antigen-presenting phagocytosis, production of inflammatory cytokines, removal of apoptotic cells, and mediating clusters between dendritic cells (DCs) and T cells. They are also increased in lesional skin of psoriasis, especially in stable plaques, and an increased ratio of M1/M2 macrophages and tumor necrosis factor-α production by macrophages are essential for development of psoriasis. The progression of skin malignancy is mediated by macrophages through promotion of tumor survival pathways via expression of cytokines and growth factors, interaction with regulatory T cells (Tregs) and myeloid-derived suppressor cells, and suppression of function of tumor-infiltrating T cells by immunosuppressive cytokines and programmed death-ligand (PD-L)1. Fibroblasts play important roles in development and maintenance of AD lesions through expression of CC chemokine ligand (CCL)17, CCL11, CCL26, C-X-C motif chemokine ligand (CXCL)12, CCL19, and periostin, interacting with T helper (Th)2 cells, natural killer T (NKT) cells, DCs, and keratinocytes. They also play important roles in psoriasis, expressing interleukin (IL)-8 and vascular endothelial growth factor, production of fibronectin, and changes in the proteomic profiles. Fibroblasts have a critical role in the progression skin malignancy via expression of cytokines, suppression natural killer (NK) functions, and establishment of Th2-dominant microenvironment. Thus, cross talk among macrophages, fibroblasts, and migratory immune cells including T cells, DCs, and NK cells in skin diseases is important and those skin-resident cells are attracting therapeutic targets in the near future.

Makoto Sugaya

Published: August 31, 2021 Explor Immunol. 2021;1:226–242
DOI: https://doi.org/10.37349/ei.2021.00015
This article belongs to the special issue Cross Talk Among Skin Cells and Immune Cells

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There are various types of skin immune responses including inflammatory skin diseases and skin malignancy. Macrophages and fibroblasts are skin resident cells that had been overlooked in terms of immunological research targets. In this review, cross talk among macrophages, fibroblasts, and migratory immune cells in skin diseases such as atopic dermatitis (AD), contact hypersensitivity, psoriasis, systemic sclerosis, melanoma, and cutaneous T-cell lymphoma is described. Macrophages are important in AD by antigen-presenting phagocytosis, production of inflammatory cytokines, removal of apoptotic cells, and mediating clusters between dendritic cells (DCs) and T cells. They are also increased in lesional skin of psoriasis, especially in stable plaques, and an increased ratio of M1/M2 macrophages and tumor necrosis factor-α production by macrophages are essential for development of psoriasis. The progression of skin malignancy is mediated by macrophages through promotion of tumor survival pathways via expression of cytokines and growth factors, interaction with regulatory T cells (Tregs) and myeloid-derived suppressor cells, and suppression of function of tumor-infiltrating T cells by immunosuppressive cytokines and programmed death-ligand (PD-L)1. Fibroblasts play important roles in development and maintenance of AD lesions through expression of CC chemokine ligand (CCL)17, CCL11, CCL26, C-X-C motif chemokine ligand (CXCL)12, CCL19, and periostin, interacting with T helper (Th)2 cells, natural killer T (NKT) cells, DCs, and keratinocytes. They also play important roles in psoriasis, expressing interleukin (IL)-8 and vascular endothelial growth factor, production of fibronectin, and changes in the proteomic profiles. Fibroblasts have a critical role in the progression skin malignancy via expression of cytokines, suppression natural killer (NK) functions, and establishment of Th2-dominant microenvironment. Thus, cross talk among macrophages, fibroblasts, and migratory immune cells including T cells, DCs, and NK cells in skin diseases is important and those skin-resident cells are attracting therapeutic targets in the near future.

Open Access

Original Article

Serum profiles of tryptophan-kynurenine pathway metabolites in psoriasis

Aim: Chronic inflammation is closely associated with tryptophan (TRP)-kynurenine (KYN) metabolic pathway. However, TRP-KYN pathway has not been fully elucidated in psoriasis, a systemic inflammator [...] Read more.

Aim: Chronic inflammation is closely associated with tryptophan (TRP)-kynurenine (KYN) metabolic pathway. However, TRP-KYN pathway has not been fully elucidated in psoriasis, a systemic inflammatory disease with skin lesions and extracutaneous manifestations. Herein, we studied comprehensively serum profiles of TRP-KYN pathway metabolites in psoriatic patients (PSOs) to clarify the involvement of this pathway in the pathophysiology of psoriasis and to evaluate serum biomarkers reflecting systemic inflammation in PSOs. Methods: The concentrations of main TRP metabolites, TRP, KYN, 3-hydroxykynurenine (3HK), kynurenic acid (KYNA), 3-hydroxyanthranilic acid (3HAA), and anthranilic acid (AA), were determined by high-performance liquid chromatography in the sera from 65 PSOs and 35 healthy controls (HCs). The levels of these metabolites and the ratios of metabolites were compared between these subjects. The correlations between these values and the psoriasis area severity index (PASI) scores were analyzed. Skin samples from PSOs and HCs were subjected to immunohistochemical staining for kynureninase, catabolic enzyme from KYN or 3HK to downstream. Cytokine concentrations were comprehensively measured in the same samples and the correlations between the cytokine levels and TRP-KYN pathway metabolite levels were examined. Results: Serum TRP, KYN, and KYNA concentrations were lower and the 3HAA concentrations were higher in PSOs than in HCs. The ratios of 3HK/KYN, 3HAA/3HK, and 3HK/AA were higher in PSOs than in HCs. The AA levels and the ratio of AA/KYN were weakly positively correlated, and TRP, KYNA, and 3HK levels and the ratios of KYNA/KYN and 3HAA/AA were weakly negatively correlated with the PASI scores. The AA, KYN, and KYNA levels were positively correlated with the interferon gamma-induced protein 10 (IP-10) concentrations. Kynureninase expression was enhanced in the epidermis, both involved and uninvolved skin. Conclusions: Serum profiles of TRP-KYN pathway metabolites differed between PSOs and HCs. TRP-KYN pathway-associated processes, including kynureninase activation, may be involved in the pathogenesis of psoriasis, and thus serve as targets for psoriasis therapy.

Mariko Seishima ... Kuniaki Saito

Published: October 31, 2021 Explor Immunol. 2021;1:258–268
DOI: https://doi.org/10.37349/ei.2021.00017
This article belongs to the special issue Cross Talk Among Skin Cells and Immune Cells

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Aim: Chronic inflammation is closely associated with tryptophan (TRP)-kynurenine (KYN) metabolic pathway. However, TRP-KYN pathway has not been fully elucidated in psoriasis, a systemic inflammatory disease with skin lesions and extracutaneous manifestations. Herein, we studied comprehensively serum profiles of TRP-KYN pathway metabolites in psoriatic patients (PSOs) to clarify the involvement of this pathway in the pathophysiology of psoriasis and to evaluate serum biomarkers reflecting systemic inflammation in PSOs. Methods: The concentrations of main TRP metabolites, TRP, KYN, 3-hydroxykynurenine (3HK), kynurenic acid (KYNA), 3-hydroxyanthranilic acid (3HAA), and anthranilic acid (AA), were determined by high-performance liquid chromatography in the sera from 65 PSOs and 35 healthy controls (HCs). The levels of these metabolites and the ratios of metabolites were compared between these subjects. The correlations between these values and the psoriasis area severity index (PASI) scores were analyzed. Skin samples from PSOs and HCs were subjected to immunohistochemical staining for kynureninase, catabolic enzyme from KYN or 3HK to downstream. Cytokine concentrations were comprehensively measured in the same samples and the correlations between the cytokine levels and TRP-KYN pathway metabolite levels were examined. Results: Serum TRP, KYN, and KYNA concentrations were lower and the 3HAA concentrations were higher in PSOs than in HCs. The ratios of 3HK/KYN, 3HAA/3HK, and 3HK/AA were higher in PSOs than in HCs. The AA levels and the ratio of AA/KYN were weakly positively correlated, and TRP, KYNA, and 3HK levels and the ratios of KYNA/KYN and 3HAA/AA were weakly negatively correlated with the PASI scores. The AA, KYN, and KYNA levels were positively correlated with the interferon gamma-induced protein 10 (IP-10) concentrations. Kynureninase expression was enhanced in the epidermis, both involved and uninvolved skin. Conclusions: Serum profiles of TRP-KYN pathway metabolites differed between PSOs and HCs. TRP-KYN pathway-associated processes, including kynureninase activation, may be involved in the pathogenesis of psoriasis, and thus serve as targets for psoriasis therapy.

Open Access

Review

Immune responses induced by different vaccine platforms against coronavirus disease-19

There have been significant developments in the design of nanostructured scaffolds for eliciting robust immune responses named vaccine. The technique is to produce strong immune responses is to mani [...] Read more.

Eknath D. Ahire, Sanjay J. Kshirsagar

Published: October 31, 2021 Explor Immunol. 2021;1:243–257
DOI: https://doi.org/10.37349/ei.2021.00016
This article belongs to the special issue Vaccine-induced Immune Responses Against SARS-CoV-2 Infections

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Times Cited: 6

Open Access

Original Article

The two faces of mast cells in vitiligo pathogenesis

Aim: Previously, we reported increased number of T helper 17 (Th17) cells in vitiligo. However, in our recent study, tryptase and interleukin (IL)17 double positive cells which identified by polycl [...] Read more.

Ichiro Katayama ... Mari Wataya-Kaneda

Published: October 31, 2021 Explor Immunol. 2021;1:269–284
DOI: https://doi.org/10.37349/ei.2021.00018
This article belongs to the special issue Cross Talk Among Skin Cells and Immune Cells

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Review

Skin and immune cells crosstalk via circadian regulations

Both innate and adaptive immune cells exist in the skin, predominantly in the dermis layer. Recent studies have focused on how and which circadian rhythms contribute to maintain good health. Over re [...] Read more.

Kanami Orihara

Published: October 31, 2021 Explor Immunol. 2021;1:285–294
DOI: https://doi.org/10.37349/ei.2021.00019
This article belongs to the special issue Cross Talk Among Skin Cells and Immune Cells

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Open Access

Review

Viral vector-based vaccines against SARS-CoV-2

Viral vectors have been frequently applied for vaccine development. It has also been the case for vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to tackle the coronavi [...] Read more.

Kenneth Lundstrom

Published: October 31, 2021 Explor Immunol. 2021;1:295–308
DOI: https://doi.org/10.37349/ei.2021.00020
This article belongs to the special issue Vaccine-induced Immune Responses Against SARS-CoV-2 Infections

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Times Cited: 4

Open Access

Review

COVID-19 vaccine and immune response

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; βCoV), the causative agent of coronavirus disease 2019 (COVID-19), causes severe lower respiratory tract infections and acute [...] Read more.

Sevilay Hintistan, Hatice Demirağ

Published: December 31, 2021 Explor Immunol. 2021;1:341–355
DOI: https://doi.org/10.37349/ei.2021.00023
This article belongs to the special issue Vaccine-induced Immune Responses Against SARS-CoV-2 Infections

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Open Access

Review

Preeclampsia—an immune disease? An epidemiologic narrative

The maternal syndrome preeclampsia is triggered by syncytiotrophoblast (STB) stress; the heterogeneity of the syndrome is caused by the different pathways leading to this STB stress. Inflammation pl [...] Read more.

The maternal syndrome preeclampsia is triggered by syncytiotrophoblast (STB) stress; the heterogeneity of the syndrome is caused by the different pathways leading to this STB stress. Inflammation plays a pivotal role in the pathogenesis of preeclampsia. While, the immune system at large is therefore intimately involved in the causation of this heterogeneous syndrome, the role of the adaptive immune system is more controversial. The classic paradigm placed preeclampsia as the disease of the nulliparous pregnant women. Up to the later part of the 20th century, human reproduction, particularly in Western societies, was characterised by a low rate of pre-marital sex, and the great majority of children being born within one stable sexual relationship. More prolonged periods of regular sexual intercourse within a stable relationship have been demonstrated to reduce the risk of preeclampsia and fetal growth restriction. Primarily animal studies have indeed shown that repetitive sperm exposure leads to partner specific mucosal tolerance. Societal changes made partner change over the reproductive period of individual women extremely common. For the adaptive immune system of multiparous women, being pregnant in a new sexual relationship (primipaternity) would represent being faced with a new “hemi-allograft”. In these pregnancies, potential couple-specific immune “maladaptation” could lead to the superficial cytotrophoblast invasion of the spiral arteries, known to be associated with early-onset preeclampsia. Having a new pregnancy in a different relationship does indeed increase the risk for this type of preeclampsia. Large epidemiologic population studies identified prolonged birth interval but not “primipaternity” as a risk factor for preeclampsia in multiparous women. This apparent contradiction is explained by the fact that the great majority of preeclampsia cases in these population studies involve term preeclampsia. In late-onset preeclampsia, the far more common phenotype of the syndrome, STB stress is not caused by lack of proper spiral artery modification, but involves maternal genetic predisposition to cardiovascular and metabolic disease, with in particular obesity/metabolic syndrome representing major players. Partner or couple specific issues are not detectable in this disease phenotype.

Gustaaf Albert Dekker, Pierre Yves Robillard

Published: December 31, 2021 Explor Immunol. 2021;1:325–340
DOI: https://doi.org/10.37349/ei.2021.00022
This article belongs to the special issue Human Reproduction: Involvement of the Immune System

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The maternal syndrome preeclampsia is triggered by syncytiotrophoblast (STB) stress; the heterogeneity of the syndrome is caused by the different pathways leading to this STB stress. Inflammation plays a pivotal role in the pathogenesis of preeclampsia. While, the immune system at large is therefore intimately involved in the causation of this heterogeneous syndrome, the role of the adaptive immune system is more controversial. The classic paradigm placed preeclampsia as the disease of the nulliparous pregnant women. Up to the later part of the 20th century, human reproduction, particularly in Western societies, was characterised by a low rate of pre-marital sex, and the great majority of children being born within one stable sexual relationship. More prolonged periods of regular sexual intercourse within a stable relationship have been demonstrated to reduce the risk of preeclampsia and fetal growth restriction. Primarily animal studies have indeed shown that repetitive sperm exposure leads to partner specific mucosal tolerance. Societal changes made partner change over the reproductive period of individual women extremely common. For the adaptive immune system of multiparous women, being pregnant in a new sexual relationship (primipaternity) would represent being faced with a new “hemi-allograft”. In these pregnancies, potential couple-specific immune “maladaptation” could lead to the superficial cytotrophoblast invasion of the spiral arteries, known to be associated with early-onset preeclampsia. Having a new pregnancy in a different relationship does indeed increase the risk for this type of preeclampsia. Large epidemiologic population studies identified prolonged birth interval but not “primipaternity” as a risk factor for preeclampsia in multiparous women. This apparent contradiction is explained by the fact that the great majority of preeclampsia cases in these population studies involve term preeclampsia. In late-onset preeclampsia, the far more common phenotype of the syndrome, STB stress is not caused by lack of proper spiral artery modification, but involves maternal genetic predisposition to cardiovascular and metabolic disease, with in particular obesity/metabolic syndrome representing major players. Partner or couple specific issues are not detectable in this disease phenotype.

Open Access

Review

Immunoregulation in the testis and its implication in fertility and infections

The testis is designated as one of the immune previleged sites in the body and harbours a unique immunoregulatory environment, which is important for preventing an immune response against sperm anti [...] Read more.

Kushaan Khambata ... Satish K. Gupta

Published: December 31, 2021 Explor Immunol. 2021;1:309–324
DOI: https://doi.org/10.37349/ei.2021.00021
This article belongs to the special issue Human Reproduction: Involvement of the Immune System

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Open Access

Review

Vaccine-induced immune responses against SARS-CoV-2 infections

Vaccination against coronavirus disease 2019 (COVID-19) is one of the most effective tools to curb the pandemic. Multiple vaccine candidates based on different platforms are available for emergency [...] Read more.

Mandeep Garg ... Suruchi Garg

Published: December 31, 2021 Explor Immunol. 2021;1:356–373
DOI: https://doi.org/10.37349/ei.2021.00024
This article belongs to the special issue Vaccine-induced Immune Responses Against SARS-CoV-2 Infections

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Open Access

Review

Activation of mucosal immunity and novel prophylactic and therapeutic strategy in combating COVID-19

Coronavirus disease 2019 (COVID-19) emerges as an expeditiously growing pandemic, in the human population caused by the highly transmissible RNA virus severe acute respiratory syndrome of coronaviru [...] Read more.

Coronavirus disease 2019 (COVID-19) emerges as an expeditiously growing pandemic, in the human population caused by the highly transmissible RNA virus severe acute respiratory syndrome of coronavirus 2 (SARS-CoV-2). Prognosis of SARS-CoV-2 infection predominantly occurs at the angiotensin-converting enzyme 2 receptor and transmembrane protease serine type 2 positive (ACE2 + TMPRSS2)+ epithelial cells of the mucosal surface like nasal, oral mucosae, and/or the conjunctival surface of the eye where it has interacted along with the immune system. The primary host response towards the pathogen starts from an immune microenvironment of nasopharynx-associated lymphoid tissue (NALT) and mucosa-associated lymphoid tissue (MALT). The presence of exhausted lymphocytes, lymphopenia, pneumonia and cytokine storm is the hallmark of COVID-19. The multifaceted nature of co-morbidity factors like obesity and type 2 diabetes and its effects on immunity can alter the pathogenesis of SARS-CoV-2 infection. Adipose tissue is a crucial endocrine organ that secretes a plethora of factors like adipokines, cytokines, and chemokines that have a profound impact on metabolism and augments the expression of mucosal pro-inflammatory cytokines, like tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and the interleukin-12 (IL-12)/IL-23. Mucosal immunization could be a superior approach to activate mucosal and systemic immune responses against pathogenic invasion at mucosal surface entry ports. Mucosal vaccines are also able to generate strong systemic humoral immunity—required to neutralize any virus particle that dodges the primary immune response. To develop an efficient vaccine against mucosal pathogens, considering the designing of the delivery route, immunomodulatory features, and adjuvants are very important. In this article, we further provide evidence to understand the significant role of mucosal immunity, along with secretory and circulating immunoglobulin A (IgA) antibodies in generating a novel mucosal vaccine against COVID-19. Moreover, along with mucosal vaccines, we should look for combination treatment strategies with plant bioactive molecules. Glycan-binding lectins against viral proteins for targeted activation of mucosal immune response are one of such examples. This might play a promising role to halt this emerging virus.

Swapan K. Chatterjee ... Maria Nilda M. Munoz

Published: December 31, 2021 Explor Immunol. 2021;1:374–397
DOI: https://doi.org/10.37349/ei.2021.00025
This article belongs to the special issue Vaccine-induced Immune Responses Against SARS-CoV-2 Infections

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Coronavirus disease 2019 (COVID-19) emerges as an expeditiously growing pandemic, in the human population caused by the highly transmissible RNA virus severe acute respiratory syndrome of coronavirus 2 (SARS-CoV-2). Prognosis of SARS-CoV-2 infection predominantly occurs at the angiotensin-converting enzyme 2 receptor and transmembrane protease serine type 2 positive (ACE2 + TMPRSS2)+ epithelial cells of the mucosal surface like nasal, oral mucosae, and/or the conjunctival surface of the eye where it has interacted along with the immune system. The primary host response towards the pathogen starts from an immune microenvironment of nasopharynx-associated lymphoid tissue (NALT) and mucosa-associated lymphoid tissue (MALT). The presence of exhausted lymphocytes, lymphopenia, pneumonia and cytokine storm is the hallmark of COVID-19. The multifaceted nature of co-morbidity factors like obesity and type 2 diabetes and its effects on immunity can alter the pathogenesis of SARS-CoV-2 infection. Adipose tissue is a crucial endocrine organ that secretes a plethora of factors like adipokines, cytokines, and chemokines that have a profound impact on metabolism and augments the expression of mucosal pro-inflammatory cytokines, like tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and the interleukin-12 (IL-12)/IL-23. Mucosal immunization could be a superior approach to activate mucosal and systemic immune responses against pathogenic invasion at mucosal surface entry ports. Mucosal vaccines are also able to generate strong systemic humoral immunity—required to neutralize any virus particle that dodges the primary immune response. To develop an efficient vaccine against mucosal pathogens, considering the designing of the delivery route, immunomodulatory features, and adjuvants are very important. In this article, we further provide evidence to understand the significant role of mucosal immunity, along with secretory and circulating immunoglobulin A (IgA) antibodies in generating a novel mucosal vaccine against COVID-19. Moreover, along with mucosal vaccines, we should look for combination treatment strategies with plant bioactive molecules. Glycan-binding lectins against viral proteins for targeted activation of mucosal immune response are one of such examples. This might play a promising role to halt this emerging virus.

Open Access

Review

A unique vaccine for birth control and treatment of advanced stage cancers secreting ectopically human chorionic gonadotropin

This article is a tribute and homage to Gerard Chaouat who invited me to contribute this article. My years in France have remained very memorable to me. Reviewed briefly is the vaccine that was made [...] Read more.

Gursaran P. Talwar ... Krishna M. Ella

Published: December 31, 2021 Explor Immunol. 2021;1:398–405
DOI: https://doi.org/10.37349/ei.2021.00026
This article belongs to the special issue Human Reproduction: Involvement of the Immune System

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Open Access

Review

Progesterone induced blocking factor in health and disease

The foetus expressing paternal antigens ought to be “rejected” by the maternal immune system. However, the immunological relationship of the mother and the foetus does not follow the rules of transplantation immunology. Matern [...] Read more.

The foetus expressing paternal antigens ought to be “rejected” by the maternal immune system. However, the immunological relationship of the mother and the foetus does not follow the rules of transplantation immunology. Maternal immune functions are re-adjusted during pregnancy, to create a tolerant environment for the developing foetus. Progesterone and its downstream mediator; the progesterone induced blocking factor (PIBF) are important in this process. The mRNA transcribed from the PIBF1 gene contains 18 exons, and codes for a 90 kDa protein. The 90 kDa form is associated with the centrosome and plays a role in cell cycle regulation, while smaller isoforms produced by alternative spicing are secreted, and bind to the glycosylphosphatidylinositol (GPI) anchored PIBF receptor. Upon ligation, the former forms a heterodimer with the alpha chain of the interleukin-4 (IL-4) receptor and activates the Janus kinase/signal transducers and activators of transcription (Jak/STAT) pathway, via which, PIBF induces increased production of T helper2 (Th2) cytokines. PIBF regulates natural killer (NK) cytotoxicity, by inhibiting perforin release from the cytoplasmic granules of NK cells. During normal human pregnancy, the serum concentrations of PIBF increase with gestational age, and lower than normal serum levels predict spontaneous pregnancy termination. Depletion of PIBF during the peri-implantation period in mice, results in lower implantation and increased resorption rates, together with increased decidual and peripheral NK activity, downregulation of the genes implicated in T cell activation in CD4+ cells, and Th1 differentiation of the T cells. PIBF is expressed in rapidly proliferating immature cells as well as several tumours, and regulates invasion. The PIBF gene has been identified in the chromosomal region 13q21-q22—which is a common site for somatic deletions in a variety of malignant tumours. These data suggest that PIBF might be involved in tumorigenesis.

Julia Szekeres-Bartho

Published: December 31, 2021 Explor Immunol. 2021;1:406–417
DOI: https://doi.org/10.37349/ei.2021.00027
This article belongs to the special issue Human Reproduction: Involvement of the Immune System

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The foetus expressing paternal antigens ought to be “rejected” by the maternal immune system. However, the immunological relationship of the mother and the foetus does not follow the rules of transplantation immunology. Maternal immune functions are re-adjusted during pregnancy, to create a tolerant environment for the developing foetus. Progesterone and its downstream mediator; the progesterone induced blocking factor (PIBF) are important in this process. The mRNA transcribed from the PIBF1 gene contains 18 exons, and codes for a 90 kDa protein. The 90 kDa form is associated with the centrosome and plays a role in cell cycle regulation, while smaller isoforms produced by alternative spicing are secreted, and bind to the glycosylphosphatidylinositol (GPI) anchored PIBF receptor. Upon ligation, the former forms a heterodimer with the alpha chain of the interleukin-4 (IL-4) receptor and activates the Janus kinase/signal transducers and activators of transcription (Jak/STAT) pathway, via which, PIBF induces increased production of T helper2 (Th2) cytokines. PIBF regulates natural killer (NK) cytotoxicity, by inhibiting perforin release from the cytoplasmic granules of NK cells. During normal human pregnancy, the serum concentrations of PIBF increase with gestational age, and lower than normal serum levels predict spontaneous pregnancy termination. Depletion of PIBF during the peri-implantation period in mice, results in lower implantation and increased resorption rates, together with increased decidual and peripheral NK activity, downregulation of the genes implicated in T cell activation in CD4+ cells, and Th1 differentiation of the T cells. PIBF is expressed in rapidly proliferating immature cells as well as several tumours, and regulates invasion. The PIBF gene has been identified in the chromosomal region 13q21-q22—which is a common site for somatic deletions in a variety of malignant tumours. These data suggest that PIBF might be involved in tumorigenesis.

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Crosstalk between keratinocytes and immune cells in inflammatory skin diseases

Cutaneous homeostasis is maintained by dynamic cellular communications between different cell types in the skin through interactions with various mediators, including cytokines, chemokines and antim [...] Read more.

Xinhui Ni, Yuping Lai

Published: December 31, 2021 Explor Immunol. 2021;1:418–431
DOI: https://doi.org/10.37349/ei.2021.00028
This article belongs to the special issue Cross Talk Among Skin Cells and Immune Cells

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New variants of SARS-CoV-2, vaccine immune response and the Brazilian reality

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a highly pathogenic β-coronavirus, is the etiologic agent of coronavirus disease 2019 (COVID-19), which gave rise to a diffi [...] Read more.

Marileia Chaves Andrade ... Hellen Oliveira Rosa

Published: December 31, 2021 Explor Immunol. 2021;1:432–439
DOI: https://doi.org/10.37349/ei.2021.00029
This article belongs to the special issue Vaccine-induced Immune Responses Against SARS-CoV-2 Infections

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