Jacques C. Mbongue, E. Vanterpool, A. Firek, W. Langridge
Bacterial lipopolysaccharides (LPS), also referred to as endotoxins, are major outer surface membrane components present on almost all Gram-negative bacteria and are major determinants of sepsis-related clinical complications including septic shock. LPS acts as a strong stimulator of innate or natural immunity in a wide variety of eukaryotic species ranging from insects to humans including specific effects on the adaptive immune system. However, following immune stimulation, lipopolysaccharide can induce tolerance which is an essential immune-homeostatic response that prevents overactivation of the inflammatory response. The tolerance induced by LPS is a state of reduced immune responsiveness due to persistent and repeated challenges, resulting in decreased expression of pro-inflammatory modulators and up-regulation of antimicrobials and other mediators that promote a reduction of inflammation. The presence of environmental-derived LPS may play a key role in decreasing autoimmune diseases and gut tolerance to the plethora of ingested antigens. The use of LPS may be an important immune adjuvant as demonstrated by the promotion of IDO1 increase when present in the fusion protein complex of CTB-INS (a chimera of the cholera toxin B subunit linked to proinsulin) that inhibits human monocyte-derived DC (moDC) activation, which may act through an IDO1-dependent pathway. The resultant state of DC tolerance can be further enhanced by the presence of residual E. coli lipopolysaccharide (LPS) which is almost always present in partially purified CTB-INS preparations. The approach to using an adjuvant with an autoantigen in immunotherapy promises effective treatment for devastating tissue-specific autoimmune diseases like multiple sclerosis (MS) and type 1 diabetes (T1D).
{"title":"Lipopolysaccharide-Induced Immunological Tolerance in Monocyte-Derived Dendritic Cells","authors":"Jacques C. Mbongue, E. Vanterpool, A. Firek, W. Langridge","doi":"10.3390/immuno2030030","DOIUrl":"https://doi.org/10.3390/immuno2030030","url":null,"abstract":"Bacterial lipopolysaccharides (LPS), also referred to as endotoxins, are major outer surface membrane components present on almost all Gram-negative bacteria and are major determinants of sepsis-related clinical complications including septic shock. LPS acts as a strong stimulator of innate or natural immunity in a wide variety of eukaryotic species ranging from insects to humans including specific effects on the adaptive immune system. However, following immune stimulation, lipopolysaccharide can induce tolerance which is an essential immune-homeostatic response that prevents overactivation of the inflammatory response. The tolerance induced by LPS is a state of reduced immune responsiveness due to persistent and repeated challenges, resulting in decreased expression of pro-inflammatory modulators and up-regulation of antimicrobials and other mediators that promote a reduction of inflammation. The presence of environmental-derived LPS may play a key role in decreasing autoimmune diseases and gut tolerance to the plethora of ingested antigens. The use of LPS may be an important immune adjuvant as demonstrated by the promotion of IDO1 increase when present in the fusion protein complex of CTB-INS (a chimera of the cholera toxin B subunit linked to proinsulin) that inhibits human monocyte-derived DC (moDC) activation, which may act through an IDO1-dependent pathway. The resultant state of DC tolerance can be further enhanced by the presence of residual E. coli lipopolysaccharide (LPS) which is almost always present in partially purified CTB-INS preparations. The approach to using an adjuvant with an autoantigen in immunotherapy promises effective treatment for devastating tissue-specific autoimmune diseases like multiple sclerosis (MS) and type 1 diabetes (T1D).","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79675605","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}
Bruno Horta, Tomé Pereira, Rui Medeiros, F. Cerqueira
Inflammation is a key factor in cancer promotion. Tumor-associated macrophages (TAMs), as part of the tumor microenvironment, are often associated with the progression of tumors and a worse prognosis in many cancers, namely on cervical cancer. This work exhaustively summarizes the conclusions of the different studies published concerning TAMs function in cervical cancer, from in vitro studies using cancer cell lines to the clinical perspective (histological samples-based studies). Most studies have led to the conclusion that TAMs increased density is directly related to increased severity of a malignant cervical lesion. Additionally, TAMs are normally polarized into an M2 phenotype, benefiting and promoting tumor progression, resulting in a worse disease outcome. The tumor microenvironment is also a highly critical contributor that not only influences tumor natural history but also modulates the specific immune response.
{"title":"Cervical Cancer Outcome and Tumor-Associated Macrophages: Research Evidence","authors":"Bruno Horta, Tomé Pereira, Rui Medeiros, F. Cerqueira","doi":"10.3390/immuno2030028","DOIUrl":"https://doi.org/10.3390/immuno2030028","url":null,"abstract":"Inflammation is a key factor in cancer promotion. Tumor-associated macrophages (TAMs), as part of the tumor microenvironment, are often associated with the progression of tumors and a worse prognosis in many cancers, namely on cervical cancer. This work exhaustively summarizes the conclusions of the different studies published concerning TAMs function in cervical cancer, from in vitro studies using cancer cell lines to the clinical perspective (histological samples-based studies). Most studies have led to the conclusion that TAMs increased density is directly related to increased severity of a malignant cervical lesion. Additionally, TAMs are normally polarized into an M2 phenotype, benefiting and promoting tumor progression, resulting in a worse disease outcome. The tumor microenvironment is also a highly critical contributor that not only influences tumor natural history but also modulates the specific immune response.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"57 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83349045","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}
C. Pistono, Cecilia Osera, M. Monti, Chiara Boiocchi, G. Mallucci, M. Cuccia, C. Montomoli, R. Bergamaschi, A. Pascale
Multiple sclerosis (MS) is a multifactorial neurodegenerative disease. Low levels of vitamin D are a risk factor for MS and alterations in the vitamin D receptor (VDR) might be a risk factor as well. This study aimed to evaluate whether the VDR rs731236 (Taq-I) and rs4334089 (HpyCH4V) gene polymorphisms and VDR protein expression are associated with MS risk and severity. Vitamin D plasma levels were analyzed in a group of patients. Additional analyses of VDR protein expression and vitamin D levels of patients with different forms of MS (MSSS < 3 and MSSS ≥ 3) were performed. The analysis of the genotypic and allelic frequencies revealed that the rs731236 (Taq-I) gene polymorphism is significantly associated with MS presence. Although the total, cytosolic and nuclear VDR protein contents do not change between MS patients and healthy controls and between patients with different MS severity, vitamin D levels decrease in parallel with an increase in MSSS.
{"title":"Vitamin D Receptor and Its Influence on Multiple Sclerosis Risk and Severity: From Gene Polymorphisms to Protein Expression","authors":"C. Pistono, Cecilia Osera, M. Monti, Chiara Boiocchi, G. Mallucci, M. Cuccia, C. Montomoli, R. Bergamaschi, A. Pascale","doi":"10.3390/immuno2030029","DOIUrl":"https://doi.org/10.3390/immuno2030029","url":null,"abstract":"Multiple sclerosis (MS) is a multifactorial neurodegenerative disease. Low levels of vitamin D are a risk factor for MS and alterations in the vitamin D receptor (VDR) might be a risk factor as well. This study aimed to evaluate whether the VDR rs731236 (Taq-I) and rs4334089 (HpyCH4V) gene polymorphisms and VDR protein expression are associated with MS risk and severity. Vitamin D plasma levels were analyzed in a group of patients. Additional analyses of VDR protein expression and vitamin D levels of patients with different forms of MS (MSSS < 3 and MSSS ≥ 3) were performed. The analysis of the genotypic and allelic frequencies revealed that the rs731236 (Taq-I) gene polymorphism is significantly associated with MS presence. Although the total, cytosolic and nuclear VDR protein contents do not change between MS patients and healthy controls and between patients with different MS severity, vitamin D levels decrease in parallel with an increase in MSSS.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84333994","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}
Calcinosis cutis is the deposition of calcium salts in the skin and subcutaneous tissue, manifesting as variably shaped papules, nodules, and plaques that can substantially impair quality of life. The pathophysiology of calcinosis cutis involves dysregulation of proinflammatory cytokines, leukocytes, and other components of the innate immune system. In some conditions associated with calcinosis cutis, elevated serum calcium, phosphate, and vitamin D may also perturb innate immunity. The mechanisms by which these lead to cutaneous and subcutaneous calcification likely parallel those seen in vascular calcification. The role of aberrant innate immunity is further supported by the association between various autoantibodies with calcinosis cutis, such as anti-MDA5, anti-NXP2, anti-centromere, and anti-topoisomerase I. Treatments for calcinosis cutis remain limited and largely experimental, although mechanistically many therapies appear to focus on dampening innate immune responses. Further research is needed to better understand the innate immune pathophysiology and establish treatment options based on randomized-controlled trials.
{"title":"Innate Immunity in Calcinosis Cutis","authors":"Simon W. Jiang, A. J. Petty, Matilda W. Nicholas","doi":"10.3390/immuno2030027","DOIUrl":"https://doi.org/10.3390/immuno2030027","url":null,"abstract":"Calcinosis cutis is the deposition of calcium salts in the skin and subcutaneous tissue, manifesting as variably shaped papules, nodules, and plaques that can substantially impair quality of life. The pathophysiology of calcinosis cutis involves dysregulation of proinflammatory cytokines, leukocytes, and other components of the innate immune system. In some conditions associated with calcinosis cutis, elevated serum calcium, phosphate, and vitamin D may also perturb innate immunity. The mechanisms by which these lead to cutaneous and subcutaneous calcification likely parallel those seen in vascular calcification. The role of aberrant innate immunity is further supported by the association between various autoantibodies with calcinosis cutis, such as anti-MDA5, anti-NXP2, anti-centromere, and anti-topoisomerase I. Treatments for calcinosis cutis remain limited and largely experimental, although mechanistically many therapies appear to focus on dampening innate immune responses. Further research is needed to better understand the innate immune pathophysiology and establish treatment options based on randomized-controlled trials.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"39 8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73416443","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}
IgG4-related disease (RD) is a proposed concept of systemic inflammatory condition from Japanese researchers. Patients with IgG4-RD manifest several immunological and histological characterizations in the organs involved, including elevated levels of serum IgG4 and lympho-plasmacytic infiltration, storiform fibrosis, IgG4-positive plasma cells infiltration, and obstructive phlebitis. Nevertheless, the pathogenesis of IgG4-RD still remains unclear. It has been made clear that several immune cells with regulatory function play a vital part in several diseases. In particular, abnormalities in the function and proportion of regulatory T cells (Tregs) are implicated in several diseases, and their part in IgG4-RD has been investigated. This review offers an overview of the research in IgG4-RD related to Tregs. Herein, the basic information of Tregs, knowledge gained from animal models involving Tregs, and the role of IgG4-RD has been provided. We also included the immunological mechanisms of IgG4-RD based on the data accumulated so far in our hypothesis.
{"title":"Recent Progress on the Roles of Regulatory T Cells in IgG4-Related Disease","authors":"K. Uchida","doi":"10.3390/immuno2020026","DOIUrl":"https://doi.org/10.3390/immuno2020026","url":null,"abstract":"IgG4-related disease (RD) is a proposed concept of systemic inflammatory condition from Japanese researchers. Patients with IgG4-RD manifest several immunological and histological characterizations in the organs involved, including elevated levels of serum IgG4 and lympho-plasmacytic infiltration, storiform fibrosis, IgG4-positive plasma cells infiltration, and obstructive phlebitis. Nevertheless, the pathogenesis of IgG4-RD still remains unclear. It has been made clear that several immune cells with regulatory function play a vital part in several diseases. In particular, abnormalities in the function and proportion of regulatory T cells (Tregs) are implicated in several diseases, and their part in IgG4-RD has been investigated. This review offers an overview of the research in IgG4-RD related to Tregs. Herein, the basic information of Tregs, knowledge gained from animal models involving Tregs, and the role of IgG4-RD has been provided. We also included the immunological mechanisms of IgG4-RD based on the data accumulated so far in our hypothesis.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89693560","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 normal human thymus originates from the third branchial cleft as two paired anlages that descend into the thorax and fuse on the midline of the anterior–superior mediastinum. Alongside the epithelial and lymphoid components, different types of lymphoid accessory cells, stromal mesenchymal and endothelial cells migrate to, or develop in, the thymus. After reaching maximum development during early postnatal life, the human thymus decreases in size and lymphocyte output drops with age. However, thymic immunological functions persist, although they deteriorate progressively. Several major techniques were fundamental to increasing the knowledge of thymic development and function during embryogenesis, postnatal and adult life; these include immunohistochemistry, immunofluorescence, flow cytometry, in vitro colony assays, transplantation in mice models, fetal organ cultures (FTOC), re-aggregated thymic organ cultures (RTOC), and whole-organ thymic scaffolds. The thymic morphological and functional characterization, first performed in the mouse, was then extended to humans. The purpose of this overview is to provide a report on selected structural and functional biomarkers of thymic epithelial cells (TEC) involved in thymus development and lymphoid cell maturation, and on the historical aspects of their characterization, with particular attention being paid to biomarkers also involved in Thymic Epithelial Tumor (TET) pathogenesis. Moreover, a short overview of targeted therapies in TET, based on currently available experimental and clinical data and on potential future advances will be proposed.
{"title":"Structural and Functional Thymic Biomarkers Are Involved in the Pathogenesis of Thymic Epithelial Tumors: An Overview","authors":"E. Gallo, M. Ramieri, M. Marino","doi":"10.3390/immuno2020025","DOIUrl":"https://doi.org/10.3390/immuno2020025","url":null,"abstract":"The normal human thymus originates from the third branchial cleft as two paired anlages that descend into the thorax and fuse on the midline of the anterior–superior mediastinum. Alongside the epithelial and lymphoid components, different types of lymphoid accessory cells, stromal mesenchymal and endothelial cells migrate to, or develop in, the thymus. After reaching maximum development during early postnatal life, the human thymus decreases in size and lymphocyte output drops with age. However, thymic immunological functions persist, although they deteriorate progressively. Several major techniques were fundamental to increasing the knowledge of thymic development and function during embryogenesis, postnatal and adult life; these include immunohistochemistry, immunofluorescence, flow cytometry, in vitro colony assays, transplantation in mice models, fetal organ cultures (FTOC), re-aggregated thymic organ cultures (RTOC), and whole-organ thymic scaffolds. The thymic morphological and functional characterization, first performed in the mouse, was then extended to humans. The purpose of this overview is to provide a report on selected structural and functional biomarkers of thymic epithelial cells (TEC) involved in thymus development and lymphoid cell maturation, and on the historical aspects of their characterization, with particular attention being paid to biomarkers also involved in Thymic Epithelial Tumor (TET) pathogenesis. Moreover, a short overview of targeted therapies in TET, based on currently available experimental and clinical data and on potential future advances will be proposed.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83089616","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}
Clostridium perfringens, a prevalent Gram-positive bacterium, causes necrotic diseases associated with abundant life loss and economic burdens of billions of USD. The mechanism of C. perfringens-induced necrotic diseases remains largely unknown, in part, because of the lack of effective animal models and the presence of a large array of exotoxins and diverse disease manifestations from the skin and deep tissues to the gastrointestinal tract. In the light of the advancement of medical and veterinary research, a large body of knowledge is accumulating on the factors influencing C. perfringens-induced necrotic disease onset, development, and outcomes. Here, we present an overview of the key virulence factors of C. perfringens exotoxins. Subsequently, we focus on comprehensively reviewing C. perfringens-induced necrotic diseases such as myonecrosis, acute watery diarrhea, enteritis necroticans, preterm infant necrotizing enterocolitis, and chicken necrotic enteritis. We then review the current understanding on the mechanisms of myonecrosis and enteritis in relation to the immune system and intestinal microbiome. Based on these discussions, we then review current preventions and treatments of the necrotic diseases and propose potential new intervention options. The purpose of this review is to provide an updated and comprehensive knowledge on the role of the host–microbe interaction to develop new interventions against C. perfringens-induced necrotic diseases.
{"title":"Clostridium perfringens-Induced Necrotic Diseases: An Overview","authors":"Ying Fu, Tahrir Alenezi, Xiaolun Sun","doi":"10.3390/immuno2020024","DOIUrl":"https://doi.org/10.3390/immuno2020024","url":null,"abstract":"Clostridium perfringens, a prevalent Gram-positive bacterium, causes necrotic diseases associated with abundant life loss and economic burdens of billions of USD. The mechanism of C. perfringens-induced necrotic diseases remains largely unknown, in part, because of the lack of effective animal models and the presence of a large array of exotoxins and diverse disease manifestations from the skin and deep tissues to the gastrointestinal tract. In the light of the advancement of medical and veterinary research, a large body of knowledge is accumulating on the factors influencing C. perfringens-induced necrotic disease onset, development, and outcomes. Here, we present an overview of the key virulence factors of C. perfringens exotoxins. Subsequently, we focus on comprehensively reviewing C. perfringens-induced necrotic diseases such as myonecrosis, acute watery diarrhea, enteritis necroticans, preterm infant necrotizing enterocolitis, and chicken necrotic enteritis. We then review the current understanding on the mechanisms of myonecrosis and enteritis in relation to the immune system and intestinal microbiome. Based on these discussions, we then review current preventions and treatments of the necrotic diseases and propose potential new intervention options. The purpose of this review is to provide an updated and comprehensive knowledge on the role of the host–microbe interaction to develop new interventions against C. perfringens-induced necrotic diseases.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87116238","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. Arnold, U. Steffen, M. Wiesener, C. Bach, B. Spriewald, M. Lindemann
Immunoglobulin A (IgA) is the most abundant antibody isotype in humans and anti-HLA IgA was found in sera of transplant recipients. Focusing on patients awaiting kidney re-transplantation, we tested the impact of anti-HLA-class I/II IgA antibodies on graft survival. We analyzed 276 patients with and 238 without allograft failure. Eight motives of the Fcα receptor (FCAR) and Fcγ receptor were analyzed in patients with allograft failure. The distribution of anti-HLA IgA1/A2 and IgG antibodies differed significantly (p < 0.0001) between both patient groups, and IgA1 plus IgA2 antibodies were more abundant in patients with allograft failure. Allograft survival was significantly impaired if anti-HLA-class I plus II IgA was present, in the first 105 months (9 years) of follow-up (median of 43 vs. >105 months, p = 0.007). Patients with anti-HLA IgA and IgG vs. anti-HLA IgG only had a significantly shorter allograft survival within that follow-up period (88 vs. >105 months, p = 0.008). Moreover, allograft survival was shorter (p = 0.02) in carriers of GG vs. AA + AG genotypes of FCAR rs16986050. Thus, the presence of anti-HLA IgA plus IgG vs. IgG only was associated with shorter kidney allograft survival and FCAR motives may impact on graft survival.
{"title":"Correlation of Anti-HLA IgA Alloantibodies and Fc Receptor Motives with Kidney Allograft Survival","authors":"M. Arnold, U. Steffen, M. Wiesener, C. Bach, B. Spriewald, M. Lindemann","doi":"10.3390/immuno2020023","DOIUrl":"https://doi.org/10.3390/immuno2020023","url":null,"abstract":"Immunoglobulin A (IgA) is the most abundant antibody isotype in humans and anti-HLA IgA was found in sera of transplant recipients. Focusing on patients awaiting kidney re-transplantation, we tested the impact of anti-HLA-class I/II IgA antibodies on graft survival. We analyzed 276 patients with and 238 without allograft failure. Eight motives of the Fcα receptor (FCAR) and Fcγ receptor were analyzed in patients with allograft failure. The distribution of anti-HLA IgA1/A2 and IgG antibodies differed significantly (p < 0.0001) between both patient groups, and IgA1 plus IgA2 antibodies were more abundant in patients with allograft failure. Allograft survival was significantly impaired if anti-HLA-class I plus II IgA was present, in the first 105 months (9 years) of follow-up (median of 43 vs. >105 months, p = 0.007). Patients with anti-HLA IgA and IgG vs. anti-HLA IgG only had a significantly shorter allograft survival within that follow-up period (88 vs. >105 months, p = 0.008). Moreover, allograft survival was shorter (p = 0.02) in carriers of GG vs. AA + AG genotypes of FCAR rs16986050. Thus, the presence of anti-HLA IgA plus IgG vs. IgG only was associated with shorter kidney allograft survival and FCAR motives may impact on graft survival.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"15 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89578259","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}
Deepshikha Yadav, S. Agarwal, Pranav Pancham, Divya Jindal, V. Agarwal, Premshankar Kumar Dubey, S. Jha, Shalini Mani, Rachana, A. Dey, N. Jha, K. Kesari, Manisha Singh
The pathogenesis of COVID-19 is complicated by immune dysfunction. The impact of immune-based therapy in COVID-19 patients has been well documented, with some notable studies on the use of anti-cytokine medicines. However, the complexity of disease phenotypes, patient heterogeneity and the varying quality of evidence from immunotherapy studies provide problems in clinical decision-making. This review seeks to aid therapeutic decision-making by giving an overview of the immunological responses against COVID-19 disease that may contribute to the severity of the disease. We have extensively discussed theranostic methods for COVID-19 detection. With advancements in technology, bioinformatics has taken studies to a higher level. The paper also discusses the application of bioinformatics and machine learning tools for the diagnosis, vaccine design and drug repurposing against SARS-CoV-2.
{"title":"Probing the Immune System Dynamics of the COVID-19 Disease for Vaccine Designing and Drug Repurposing Using Bioinformatics Tools","authors":"Deepshikha Yadav, S. Agarwal, Pranav Pancham, Divya Jindal, V. Agarwal, Premshankar Kumar Dubey, S. Jha, Shalini Mani, Rachana, A. Dey, N. Jha, K. Kesari, Manisha Singh","doi":"10.3390/immuno2020022","DOIUrl":"https://doi.org/10.3390/immuno2020022","url":null,"abstract":"The pathogenesis of COVID-19 is complicated by immune dysfunction. The impact of immune-based therapy in COVID-19 patients has been well documented, with some notable studies on the use of anti-cytokine medicines. However, the complexity of disease phenotypes, patient heterogeneity and the varying quality of evidence from immunotherapy studies provide problems in clinical decision-making. This review seeks to aid therapeutic decision-making by giving an overview of the immunological responses against COVID-19 disease that may contribute to the severity of the disease. We have extensively discussed theranostic methods for COVID-19 detection. With advancements in technology, bioinformatics has taken studies to a higher level. The paper also discusses the application of bioinformatics and machine learning tools for the diagnosis, vaccine design and drug repurposing against SARS-CoV-2.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"32 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84669394","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}
Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors used worldwide to manage dyslipidaemia and thus limit the development of atherosclerotic disease and its complications. These atheroprotective drugs are now known to exert pleiotropic actions outside of their cholesterol-lowering activity, including altering immune cell function. Macrophages are phagocytic leukocytes that play critical functional roles in the pathogenesis of atherosclerosis and are directly targeted by statins. Early studies documented the anti-inflammatory effects of statins on macrophages, but emerging evidence suggests that these drugs can also enhance pro-inflammatory macrophage responses, creating an unresolved paradox. This review comprehensively examines the in vitro, in vivo, and clinical literature to document the statin-induced changes in macrophage polarization and immunomodulatory functions, explore the underlying mechanisms involved, and offer potential explanations for this paradox. A better understanding of the immunomodulatory actions of statins on macrophages should pave the way for the development of novel therapeutic approaches to manage atherosclerosis and other chronic diseases and conditions characterised by unresolved inflammation.
{"title":"The Immunomodulatory Effects of Statins on Macrophages","authors":"Alan Sheridan, C. Wheeler-Jones, M. Gage","doi":"10.3390/immuno2020021","DOIUrl":"https://doi.org/10.3390/immuno2020021","url":null,"abstract":"Statins are 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors used worldwide to manage dyslipidaemia and thus limit the development of atherosclerotic disease and its complications. These atheroprotective drugs are now known to exert pleiotropic actions outside of their cholesterol-lowering activity, including altering immune cell function. Macrophages are phagocytic leukocytes that play critical functional roles in the pathogenesis of atherosclerosis and are directly targeted by statins. Early studies documented the anti-inflammatory effects of statins on macrophages, but emerging evidence suggests that these drugs can also enhance pro-inflammatory macrophage responses, creating an unresolved paradox. This review comprehensively examines the in vitro, in vivo, and clinical literature to document the statin-induced changes in macrophage polarization and immunomodulatory functions, explore the underlying mechanisms involved, and offer potential explanations for this paradox. A better understanding of the immunomodulatory actions of statins on macrophages should pave the way for the development of novel therapeutic approaches to manage atherosclerosis and other chronic diseases and conditions characterised by unresolved inflammation.","PeriodicalId":55599,"journal":{"name":"Immuno-Analyse & Biologie Specialisee","volume":"34 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81047178","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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