The emergence and re-emergence of pathogens is a public-health concern, which has become more evident after the coronavirus disease 2019 (COVID-19) pandemic and the monkeypox outbreaks in early 2022. Given that vaccines are the more effective and affordable tools to control infectious diseases, the authors reviewed two heterologous effects of vaccines: the trained immunity and the cross-reactivity. Trained immunity, provided by attenuated vaccines, was exemplified in this article by the decreased the burden of COVID-19 in populations with high Bacille Calmette-Guerin (BCG) coverage. Cross-reactive responses were exemplified here by the studies which suggested that vaccinia could help controlling the monkeypox outbreak, because of common epitopes shared by orthopoxviruses. Although modern vaccination is likely to use subunit vaccines, the authors discussed how adjuvants might be the key to induce trained immunity and improve cross-reactive responses, ensuring that heterologous effects would improve the vaccine’s response.
{"title":"Trained-immunity and cross-reactivity for protection: insights from the coronavirus disease 2019 and monkeypox emergencies for vaccine development","authors":"A. Portilho, E. De Gaspari","doi":"10.37349/ei.2023.00102","DOIUrl":"https://doi.org/10.37349/ei.2023.00102","url":null,"abstract":"The emergence and re-emergence of pathogens is a public-health concern, which has become more evident after the coronavirus disease 2019 (COVID-19) pandemic and the monkeypox outbreaks in early 2022. Given that vaccines are the more effective and affordable tools to control infectious diseases, the authors reviewed two heterologous effects of vaccines: the trained immunity and the cross-reactivity. Trained immunity, provided by attenuated vaccines, was exemplified in this article by the decreased the burden of COVID-19 in populations with high Bacille Calmette-Guerin (BCG) coverage. Cross-reactive responses were exemplified here by the studies which suggested that vaccinia could help controlling the monkeypox outbreak, because of common epitopes shared by orthopoxviruses. Although modern vaccination is likely to use subunit vaccines, the authors discussed how adjuvants might be the key to induce trained immunity and improve cross-reactive responses, ensuring that heterologous effects would improve the vaccine’s response.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44793942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sneha Das, Tamanna Sharma, A. Bhardwaj, R. Srivastava
The coronavirus disease-2019 (COVID-19) pandemic is a significant threat in the modern era. Clinical studies show that the most common symptom of severe COVID-19 is viral pneumonia-induced acute respiratory distress syndrome (ARDS). The underlying mechanisms by which severe respiratory disease syndrome-coronavirus-2 (SARS-CoV-2) results in ARDS and how certain host factors confer an increased risk of developing severe disease remain unknown. Therefore, identifying the distinctive features of this severe and fatal disease and the therapeutic approaches to COVID-19-induced ARDS remains an immediate need to serve as a basis for best practice models of standardized ARDS treatment. This review article aims to comprehensively discuss the immunopathology of ARDS and provides an overview of the precise role of both the innate and adaptive immune system, with emphasis on the current treatment strategies being tested in the COVID-19-induced ARDS patients. This knowledge will supposedly help in revealing further mechanistic insights into understanding COVID-19-induced ARDS.
{"title":"COVID-19 induced ARDS: immunopathology and therapeutics","authors":"Sneha Das, Tamanna Sharma, A. Bhardwaj, R. Srivastava","doi":"10.37349/ei.2023.00101","DOIUrl":"https://doi.org/10.37349/ei.2023.00101","url":null,"abstract":"The coronavirus disease-2019 (COVID-19) pandemic is a significant threat in the modern era. Clinical studies show that the most common symptom of severe COVID-19 is viral pneumonia-induced acute respiratory distress syndrome (ARDS). The underlying mechanisms by which severe respiratory disease syndrome-coronavirus-2 (SARS-CoV-2) results in ARDS and how certain host factors confer an increased risk of developing severe disease remain unknown. Therefore, identifying the distinctive features of this severe and fatal disease and the therapeutic approaches to COVID-19-induced ARDS remains an immediate need to serve as a basis for best practice models of standardized ARDS treatment. This review article aims to comprehensively discuss the immunopathology of ARDS and provides an overview of the precise role of both the innate and adaptive immune system, with emphasis on the current treatment strategies being tested in the COVID-19-induced ARDS patients. This knowledge will supposedly help in revealing further mechanistic insights into understanding COVID-19-induced ARDS.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45974923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The Src homology 2 (SH2) and SH3 domain-containing chicken tumor virus number 10 (CT10) regulator of kinase (Crk) adaptor proteins include three cellular members that serve as integral constituents of multiple receptor-linked signal transduction pathways. CrkI and CrkII are products of alternative RNA-splicing which is transcribed from a single gene, while Crk-like (CrkL), which is highly homologous to CrkII, is encoded by a different gene. Thanks to their modular structure, the Crk adaptor proteins can simultaneously interact with activated receptors and a wide range of effector molecules, and orchestrate the assembly of complexes containing enzymes and substrates at the receptor site. They are involved in the regulation of a large number of cellular processes which control cell growth, differentiation, transformation, and apoptosis. Cell activation-dependent tyrosine phosphorylation of CrkII and CrkL serves as a major posttranslational modification mechanism that introduces conformational changes in the proteins by promoting an intramolecular interaction between the phosphotyrosine and the self SH2 domain. The resulting conformational change induces downregulation of CrkII- and CrkL-dependent biological processes. A second type of posttranslational modification mechanism regulates the structure and function of the CrkII adaptor protein by immunophilin-mediated protein isomerization. Two of the most abundant immunophilins in T lymphocytes which function as peptidyl-prolyl cis-trans isomerases (PPIases), namely cyclophilin A (CypA) and FK506-binding proteins (FKBPs), can associate with CrkII and catalyze its reciprocal cis-trans isomerization. This mechanism is of special importance for the regulation of T lymphocyte functions and for T cell-mediated immune responses, since immunophilin inhibitors, such as cyclosporin A (CsA) and FK506, function as immunosuppressive drugs that can prevent allotransplanted graft rejection. The present manuscript focuses on selected functions of Crk adaptor proteins, predominantly in T lymphocytes, and reviews in more detail the current knowledge on the immunophilin-dependent regulation of the structure and function of the CrkII adaptor protein.
{"title":"Conformational and functional regulation of the chicken tumor virus number 10 (CT10) regulator of kinase II (CrkII) adaptor protein by cyclophilin A","authors":"N. Isakov","doi":"10.37349/ei.2023.00099","DOIUrl":"https://doi.org/10.37349/ei.2023.00099","url":null,"abstract":"The Src homology 2 (SH2) and SH3 domain-containing chicken tumor virus number 10 (CT10) regulator of kinase (Crk) adaptor proteins include three cellular members that serve as integral constituents of multiple receptor-linked signal transduction pathways. CrkI and CrkII are products of alternative RNA-splicing which is transcribed from a single gene, while Crk-like (CrkL), which is highly homologous to CrkII, is encoded by a different gene. Thanks to their modular structure, the Crk adaptor proteins can simultaneously interact with activated receptors and a wide range of effector molecules, and orchestrate the assembly of complexes containing enzymes and substrates at the receptor site. They are involved in the regulation of a large number of cellular processes which control cell growth, differentiation, transformation, and apoptosis. Cell activation-dependent tyrosine phosphorylation of CrkII and CrkL serves as a major posttranslational modification mechanism that introduces conformational changes in the proteins by promoting an intramolecular interaction between the phosphotyrosine and the self SH2 domain. The resulting conformational change induces downregulation of CrkII- and CrkL-dependent biological processes. A second type of posttranslational modification mechanism regulates the structure and function of the CrkII adaptor protein by immunophilin-mediated protein isomerization. Two of the most abundant immunophilins in T lymphocytes which function as peptidyl-prolyl cis-trans isomerases (PPIases), namely cyclophilin A (CypA) and FK506-binding proteins (FKBPs), can associate with CrkII and catalyze its reciprocal cis-trans isomerization. This mechanism is of special importance for the regulation of T lymphocyte functions and for T cell-mediated immune responses, since immunophilin inhibitors, such as cyclosporin A (CsA) and FK506, function as immunosuppressive drugs that can prevent allotransplanted graft rejection. The present manuscript focuses on selected functions of Crk adaptor proteins, predominantly in T lymphocytes, and reviews in more detail the current knowledge on the immunophilin-dependent regulation of the structure and function of the CrkII adaptor protein.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46904934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Besides trauma, several pathological conditions which directly affect the normal functioning of organs, require new therapeutic strategies to repair damaged or diseased tissues. Tissue regeneration is a complex and spatiotemporal process involving a plethora of cell types, including various immune cells and stem cells in a synchronized relationship. However, individual parameters, namely ageing, obesity, diabetes, and chronic conditions, have been intrinsically correlated with poor regenerative properties of adult tissues. While vast progress has been made regarding stem cell-based therapy to direct self-healing, the immune response is still the Achilles’ heel of such strategies. Whereas the role of effector immune cells has been well defined along the regenerative process, an understanding of the behavior of the main adult stem cells, namely mesenchymal stem cells (MSCs) and hematopoietic stem and progenitor cells (HSPCs), along the different phases of the regenerative process could clarify how these stem cells can be used to positively influence the immune response. In this scope, this review highlights the main interactions between these stem cells and immune cells during tissue repair, exploring the most important regenerative properties of stem cells and correlating them with the modulation of the immune response during tissue regeneration. Furthermore, the utmost strategies used to explore how the behavior and stem cell fate are affected by specific microenvironments and/or stimuli usually found during a regenerative process, are emphasized. This clarification may provide critical insight into the molecular mechanisms by which stem cells modulate the immune response in a positive feedback loop toward tissue repair.
{"title":"Immune response: the Achilles’ heel of the stem cell-based regenerative therapies","authors":"C. S. Oliveira, F. Tavaria","doi":"10.37349/ei.2023.00100","DOIUrl":"https://doi.org/10.37349/ei.2023.00100","url":null,"abstract":"Besides trauma, several pathological conditions which directly affect the normal functioning of organs, require new therapeutic strategies to repair damaged or diseased tissues. Tissue regeneration is a complex and spatiotemporal process involving a plethora of cell types, including various immune cells and stem cells in a synchronized relationship. However, individual parameters, namely ageing, obesity, diabetes, and chronic conditions, have been intrinsically correlated with poor regenerative properties of adult tissues. While vast progress has been made regarding stem cell-based therapy to direct self-healing, the immune response is still the Achilles’ heel of such strategies. Whereas the role of effector immune cells has been well defined along the regenerative process, an understanding of the behavior of the main adult stem cells, namely mesenchymal stem cells (MSCs) and hematopoietic stem and progenitor cells (HSPCs), along the different phases of the regenerative process could clarify how these stem cells can be used to positively influence the immune response. In this scope, this review highlights the main interactions between these stem cells and immune cells during tissue repair, exploring the most important regenerative properties of stem cells and correlating them with the modulation of the immune response during tissue regeneration. Furthermore, the utmost strategies used to explore how the behavior and stem cell fate are affected by specific microenvironments and/or stimuli usually found during a regenerative process, are emphasized. This clarification may provide critical insight into the molecular mechanisms by which stem cells modulate the immune response in a positive feedback loop toward tissue repair.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46413122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Periodontal tissue destruction can cause complaints for sufferers. Inflammatory conditions of the gingiva, bleeding gums, and even tooth loss are clinical features of the destruction of the periodontal tissues. Periodontitis is an inflammatory disease involving the periodontal tissues. The prevalence of periodontium destruction increases with aging. Changes in innate and adaptive immunity that occur in the elderly also play a role in the severity of periodontitis. “Inflammaging” is a chronic inflammatory state associated with old age in humans. Periodontitis contributes to inflammaging since periodontitis in the elderly is associated with increased markers of systemic inflammation. Age-related changes also affect neutrophil function, especially antimicrobial activity, so neutrophils may become more pathological. After infiltration into the tissue, neutrophils are equipped with several antimicrobial strategies to reduce the number of antigens. Phagocytosis is the ability of neutrophils to engulf and kill microbes, but neutrophil phagocytosis is weakened in the elderly. Age-related changes affecting neutrophils, macrophages, and T cells appear to promote pathogenic immune responses and contribute to the increased prevalence of periodontal disease in aging individuals. Proper regulation of the host immune response is critical in maintaining periodontal health. This paper aims to describe the aging process and its relation to periodontal conditions.
{"title":"The aging process and its relation to periodontal conditions","authors":"Pitu Wulandari","doi":"10.37349/ei.2023.00098","DOIUrl":"https://doi.org/10.37349/ei.2023.00098","url":null,"abstract":"Periodontal tissue destruction can cause complaints for sufferers. Inflammatory conditions of the gingiva, bleeding gums, and even tooth loss are clinical features of the destruction of the periodontal tissues. Periodontitis is an inflammatory disease involving the periodontal tissues. The prevalence of periodontium destruction increases with aging. Changes in innate and adaptive immunity that occur in the elderly also play a role in the severity of periodontitis. “Inflammaging” is a chronic inflammatory state associated with old age in humans. Periodontitis contributes to inflammaging since periodontitis in the elderly is associated with increased markers of systemic inflammation. Age-related changes also affect neutrophil function, especially antimicrobial activity, so neutrophils may become more pathological. After infiltration into the tissue, neutrophils are equipped with several antimicrobial strategies to reduce the number of antigens. Phagocytosis is the ability of neutrophils to engulf and kill microbes, but neutrophil phagocytosis is weakened in the elderly. Age-related changes affecting neutrophils, macrophages, and T cells appear to promote pathogenic immune responses and contribute to the increased prevalence of periodontal disease in aging individuals. Proper regulation of the host immune response is critical in maintaining periodontal health. This paper aims to describe the aging process and its relation to periodontal conditions.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47267283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Human germinal center (GC)-associated lymphoma (HGAL) is a multi-domain adaptor protein expressed in GC B lymphocytes, T follicular helper (Tfh) cells and lymphomas derived from these cells. HGAL expression is an independent predictor of longer survival of diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin’s lymphoma (HL) patients. HGAL regulates B cell receptor (BCR) signaling and immunological synapse formation by binding to either the downstream effectors [e.g., spleen tyrosine kinase (Syk)] or other signaling regulators [e.g., growth factor receptor-bound protein 2 (Grb2)]. HGAL regulates the cytoskeleton that reshapes B cell morphology during BCR signaling and cell motility by at least two molecular mechanisms: enhanced Ras homolog gene family member A (RhoA) signaling and inhibition of myosin-actin translocation. These effects on the cytoskeleton decrease lymphoma dissemination in animal models and contribute to decreased lymphoma dissemination in patients. The latter may contribute to the association of HGAL protein expression with longer survival of patients with DLBCL and HL tumors. The ability to regulate multiple and distinct functions simultaneously in B cells implies that the HGAL protein level is tightly regulated. It was demonstrated that HGAL can be regulated by PR/SET domain 1 (PRDM1)/B lymphocyte-induced maturation protein-1 (BLIMP1) and interleukin-4 (IL-4) at the transcription level, by microRNA-155 (miR-155) at the post-transcriptional level, and by F-box protein 10 (FBXO10) at the post-translational level. Constitutive enforced expression of HGAL at physiological levels leads to lymphoid hyperplasia and DLBCL in mice. Future studies need to focus on identifying HGAL interactome, dissecting its interaction network, and understanding HGAL spatiotemporal signaling in live cells in physiological conditions. Further, the recent demonstration of HGAL expression in Tfh cells requires the determination of its function in these cells. These studies will contribute to new insights into the biology of these cellular subsets and how immune dysregulation contributes to lymphomagenesis.
{"title":"Role of an adaptor protein human germinal center-associated lymphoma (HGAL) in cell signaling and lymphomagenesis","authors":"Xiaoyu Jiang, I. Lossos","doi":"10.37349/ei.2023.00097","DOIUrl":"https://doi.org/10.37349/ei.2023.00097","url":null,"abstract":"Human germinal center (GC)-associated lymphoma (HGAL) is a multi-domain adaptor protein expressed in GC B lymphocytes, T follicular helper (Tfh) cells and lymphomas derived from these cells. HGAL expression is an independent predictor of longer survival of diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin’s lymphoma (HL) patients. HGAL regulates B cell receptor (BCR) signaling and immunological synapse formation by binding to either the downstream effectors [e.g., spleen tyrosine kinase (Syk)] or other signaling regulators [e.g., growth factor receptor-bound protein 2 (Grb2)]. HGAL regulates the cytoskeleton that reshapes B cell morphology during BCR signaling and cell motility by at least two molecular mechanisms: enhanced Ras homolog gene family member A (RhoA) signaling and inhibition of myosin-actin translocation. These effects on the cytoskeleton decrease lymphoma dissemination in animal models and contribute to decreased lymphoma dissemination in patients. The latter may contribute to the association of HGAL protein expression with longer survival of patients with DLBCL and HL tumors. The ability to regulate multiple and distinct functions simultaneously in B cells implies that the HGAL protein level is tightly regulated. It was demonstrated that HGAL can be regulated by PR/SET domain 1 (PRDM1)/B lymphocyte-induced maturation protein-1 (BLIMP1) and interleukin-4 (IL-4) at the transcription level, by microRNA-155 (miR-155) at the post-transcriptional level, and by F-box protein 10 (FBXO10) at the post-translational level. Constitutive enforced expression of HGAL at physiological levels leads to lymphoid hyperplasia and DLBCL in mice. Future studies need to focus on identifying HGAL interactome, dissecting its interaction network, and understanding HGAL spatiotemporal signaling in live cells in physiological conditions. Further, the recent demonstration of HGAL expression in Tfh cells requires the determination of its function in these cells. These studies will contribute to new insights into the biology of these cellular subsets and how immune dysregulation contributes to lymphomagenesis.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41920529","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Fujii, Shuhei Kobayashi, Ayane Ueda, Misaki Sakagami, R. Matsui, Yumeka Yamada, T. Nabe, S. Ohya
Aim: Atopic dermatitis (AD) is a pruritic, chronic inflammatory skin disease. Thymic stromal lymphopoietin (TSLP) is highly expressed in the epidermis of patients with AD and induces T helper 2 (Th2) immune responses and itching. Although the mechanism underlying the stimulus-induced TSLP production in normal keratinocytes has been intensively studied, whether the production capability of TSLP is naturally enhanced in epidermal cells in AD conditions remains unclear. Previous studies demonstrated that a deficiency of polyunsaturated fatty acid (PUFA) causes AD-like pruritic skin inflammation in special diet-fed hairless mice. The aim of the study was to examine the TSLP production capability of epidermal cells isolated from diet-induced AD mouse model and its mechanism. Methods: Epidermal cells were isolated from normal and AD mice and incubated under unstimulated culture conditions to assess spontaneous TSLP production. Messenger ribonucleic acid (mRNA) and protein levels of TSLP were determined by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Results: TSLP level was markedly increased in the skin of AD mice. When epidermal cells were isolated from AD mice and cultured without stimulation, Tslp gene expression was upregulated, and a large amount of TSLP protein was extracellularly released. Such TSLP overproduction was not observed in the epidermal cells of normal mice. TSLP overproduction in AD epidermal cells was almost completely inhibited by extracellular calcium chelation, interference with plasma membrane interaction of stromal interaction molecule 1 (STIM1), blockade of the calcium release-activated calcium (CRAC) channels Orai1 and Orai2, or treatment with a PUFA γ-linolenic acid (GLA). Conclusions: Epidermal cells isolated from AD mice can spontaneously produce TSLP through STIM/Orai-mediated calcium entry, and GLA may negatively regulate this TSLP production.
{"title":"STIM/Orai-mediated calcium entry elicits spontaneous TSLP overproduction in epidermal cells of atopic dermatitis mice","authors":"M. Fujii, Shuhei Kobayashi, Ayane Ueda, Misaki Sakagami, R. Matsui, Yumeka Yamada, T. Nabe, S. Ohya","doi":"10.37349/ei.2023.00096","DOIUrl":"https://doi.org/10.37349/ei.2023.00096","url":null,"abstract":"Aim: Atopic dermatitis (AD) is a pruritic, chronic inflammatory skin disease. Thymic stromal lymphopoietin (TSLP) is highly expressed in the epidermis of patients with AD and induces T helper 2 (Th2) immune responses and itching. Although the mechanism underlying the stimulus-induced TSLP production in normal keratinocytes has been intensively studied, whether the production capability of TSLP is naturally enhanced in epidermal cells in AD conditions remains unclear. Previous studies demonstrated that a deficiency of polyunsaturated fatty acid (PUFA) causes AD-like pruritic skin inflammation in special diet-fed hairless mice. The aim of the study was to examine the TSLP production capability of epidermal cells isolated from diet-induced AD mouse model and its mechanism.\u0000Methods: Epidermal cells were isolated from normal and AD mice and incubated under unstimulated culture conditions to assess spontaneous TSLP production. Messenger ribonucleic acid (mRNA) and protein levels of TSLP were determined by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively.\u0000Results: TSLP level was markedly increased in the skin of AD mice. When epidermal cells were isolated from AD mice and cultured without stimulation, Tslp gene expression was upregulated, and a large amount of TSLP protein was extracellularly released. Such TSLP overproduction was not observed in the epidermal cells of normal mice. TSLP overproduction in AD epidermal cells was almost completely inhibited by extracellular calcium chelation, interference with plasma membrane interaction of stromal interaction molecule 1 (STIM1), blockade of the calcium release-activated calcium (CRAC) channels Orai1 and Orai2, or treatment with a PUFA γ-linolenic acid (GLA).\u0000Conclusions: Epidermal cells isolated from AD mice can spontaneously produce TSLP through STIM/Orai-mediated calcium entry, and GLA may negatively regulate this TSLP production.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42654786","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The growth and differentiation of normal cells are controlled by protein-tyrosine kinases, which serve as receptors for a wide variety of external signals. Small protein modules called Src homology 2 (SH2) and SH3 domains mediate protein-protein interactions in signaling pathways that are triggered by protein tyrosine kinases. The SH2 domain, a protein module of around 100 amino acids, is present in tyrosine kinase targets within the cell. SH2 domains are recruited to activated and autophosphorylated growth factor receptors by directly recognizing tyrosine phosphorylation sites. Growth factor receptors and other phosphoproteins have short phosphotyrosine (pTyr)-containing sequences that are bound by SH2 domains. The SH3 domain, a distinct element of approximately 50 residues that recognizes proline-rich and hydrophobic-amino-acid-containing regions, is frequently found in SH2-containing proteins. Tyrosine kinases can be coupled to downstream targets with SH3-binding sites by proteins with SH2 and SH3 domains acting as adaptors. These intricate and precise biochemical signaling pathways result in the regulation of gene expression, cytoskeletal architecture, and cell metabolism. The role of SH2/SH3 proteins in T cell signaling will be discussed. A special focus will be on the role of the hematopoietic signal transducer with SH2/SH3 domains, Vav1, in health and cancer.
{"title":"Role of Vav1, a hematopoietic signal transduction molecule, as an adaptor protein in health and disease","authors":"S. Katzav","doi":"10.37349/ei.2023.00095","DOIUrl":"https://doi.org/10.37349/ei.2023.00095","url":null,"abstract":"The growth and differentiation of normal cells are controlled by protein-tyrosine kinases, which serve as receptors for a wide variety of external signals. Small protein modules called Src homology 2 (SH2) and SH3 domains mediate protein-protein interactions in signaling pathways that are triggered by protein tyrosine kinases. The SH2 domain, a protein module of around 100 amino acids, is present in tyrosine kinase targets within the cell. SH2 domains are recruited to activated and autophosphorylated growth factor receptors by directly recognizing tyrosine phosphorylation sites. Growth factor receptors and other phosphoproteins have short phosphotyrosine (pTyr)-containing sequences that are bound by SH2 domains. The SH3 domain, a distinct element of approximately 50 residues that recognizes proline-rich and hydrophobic-amino-acid-containing regions, is frequently found in SH2-containing proteins. Tyrosine kinases can be coupled to downstream targets with SH3-binding sites by proteins with SH2 and SH3 domains acting as adaptors. These intricate and precise biochemical signaling pathways result in the regulation of gene expression, cytoskeletal architecture, and cell metabolism. The role of SH2/SH3 proteins in T cell signaling will be discussed. A special focus will be on the role of the hematopoietic signal transducer with SH2/SH3 domains, Vav1, in health and cancer.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42872837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Surgery, chemotherapy, radiation therapy, and immunotherapy are potential therapeutic choices for many malignant and metastatic cancers. Despite adverse side effects and pain, surgery and chemotherapy continue to be the most common cancer treatments. However, patients treated with immunotherapy had better cancer control than those who got other treatments. There are two methods to activate immunological pathways: systemically and locally. To modify the tumor microenvironment (TME), the former uses systemic cytokine/chemokine (CK) delivery, whilst the latter uses immunological checkpoints or small molecule inhibitors. Organic and inorganic nanomaterials (NMs) enhanced the efficacy of cancer immunotherapy. NMs can transmit drugs, peptides, antigens, antibodies, whole cell membranes, etc. Surface-modified NMs precisely target and enter the tissues. The inner core of surface-modified NMs is composed of chemicals with limited bioavailability and biocompatibility, resulting in prolonged blood retention and decreased renal clearance. These platforms hinder or prevent many immune cell activities and modify the TME, enhancing the efficiency of cancer immunotherapy. By inhibiting CK/CK receptor signaling, cell migration and other immune responses could be controlled. Developing CK-targeted nanoparticles (NPs) that inhibit CK signaling or take advantage of the ligand-receptor connection is possible. Surface chemical modification of NMs with CKs or specific peptides has several medicinal applications, including tissue-specific drug delivery and limited cell migration in cancer-afflicted conditions. This review covers current developments in the role of different groups of CK-loaded NP in tumor therapy targeting immune cells and cancer. It also covers the role of NP targeting CK signaling which aids in immunogenic cell death (ICD) and induction of antitumor immunity. In addition, CK gene silencing and its capacity to prevent cancer metastasis as well as inhibition of immune cell migration to modulate the TME are discussed.
{"title":"Chemokine-targeted nanoparticles: stimulation of the immune system in cancer immunotherapy","authors":"Ranjeet Singh, Prateek Srivastava, P. Manna","doi":"10.37349/ei.2023.00093","DOIUrl":"https://doi.org/10.37349/ei.2023.00093","url":null,"abstract":"Surgery, chemotherapy, radiation therapy, and immunotherapy are potential therapeutic choices for many malignant and metastatic cancers. Despite adverse side effects and pain, surgery and chemotherapy continue to be the most common cancer treatments. However, patients treated with immunotherapy had better cancer control than those who got other treatments. There are two methods to activate immunological pathways: systemically and locally. To modify the tumor microenvironment (TME), the former uses systemic cytokine/chemokine (CK) delivery, whilst the latter uses immunological checkpoints or small molecule inhibitors. Organic and inorganic nanomaterials (NMs) enhanced the efficacy of cancer immunotherapy. NMs can transmit drugs, peptides, antigens, antibodies, whole cell membranes, etc. Surface-modified NMs precisely target and enter the tissues. The inner core of surface-modified NMs is composed of chemicals with limited bioavailability and biocompatibility, resulting in prolonged blood retention and decreased renal clearance. These platforms hinder or prevent many immune cell activities and modify the TME, enhancing the efficiency of cancer immunotherapy. By inhibiting CK/CK receptor signaling, cell migration and other immune responses could be controlled. Developing CK-targeted nanoparticles (NPs) that inhibit CK signaling or take advantage of the ligand-receptor connection is possible. Surface chemical modification of NMs with CKs or specific peptides has several medicinal applications, including tissue-specific drug delivery and limited cell migration in cancer-afflicted conditions. This review covers current developments in the role of different groups of CK-loaded NP in tumor therapy targeting immune cells and cancer. It also covers the role of NP targeting CK signaling which aids in immunogenic cell death (ICD) and induction of antitumor immunity. In addition, CK gene silencing and its capacity to prevent cancer metastasis as well as inhibition of immune cell migration to modulate the TME are discussed.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46938746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mesenchymal stem/stromal cells (MSCs) are known as multipotent cells due to their ability to differentiate into various cell lineages of mesoderm origin. Recent developments in stem cell biology have provided a new ray of hope for the treatment of diseases and disorders that are yet to be treated. These cells have been widely used in animals and clinical trials in humans. To date, there are more than 920 clinical trials on humans related to MSCs as cell-based therapy in various conditions. The purpose of this review is to provide a summary of the characteristics of MSCs, evaluate their immunological properties, activation of MSCs that dictate their soluble factors, possible pathway, and mechanisms involved by MSCs and immune cell interaction, and various application of MSCs in different diseases.
{"title":"Mesenchymal stem cells—the master immunomodulators","authors":"Mehak Vohra, S. Arora","doi":"10.37349/ei.2023.00092","DOIUrl":"https://doi.org/10.37349/ei.2023.00092","url":null,"abstract":"Mesenchymal stem/stromal cells (MSCs) are known as multipotent cells due to their ability to differentiate into various cell lineages of mesoderm origin. Recent developments in stem cell biology have provided a new ray of hope for the treatment of diseases and disorders that are yet to be treated. These cells have been widely used in animals and clinical trials in humans. To date, there are more than 920 clinical trials on humans related to MSCs as cell-based therapy in various conditions. The purpose of this review is to provide a summary of the characteristics of MSCs, evaluate their immunological properties, activation of MSCs that dictate their soluble factors, possible pathway, and mechanisms involved by MSCs and immune cell interaction, and various application of MSCs in different diseases.","PeriodicalId":93552,"journal":{"name":"Exploration of immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42109290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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