Immune NetworkPub Date : 2023-01-30eCollection Date: 2023-04-01DOI: 10.4110/in.2023.23.e14
Young-Ju Kang, Hee Jun Cho, Yunhee Lee, Arum Park, Mi Jeong Kim, In Cheul Jeung, Yong-Wook Jung, Haiyoung Jung, Inpyo Choi, Hee Gu Lee, Suk Ran Yoon
{"title":"IL-17A and Th17 Cells Contribute to Endometrial Cell Survival by Inhibiting Apoptosis and NK Cell Mediated Cytotoxicity of Endometrial Cells via ERK1/2 Pathway.","authors":"Young-Ju Kang, Hee Jun Cho, Yunhee Lee, Arum Park, Mi Jeong Kim, In Cheul Jeung, Yong-Wook Jung, Haiyoung Jung, Inpyo Choi, Hee Gu Lee, Suk Ran Yoon","doi":"10.4110/in.2023.23.e14","DOIUrl":"10.4110/in.2023.23.e14","url":null,"abstract":"<p><p>Immune status including the immune cells and cytokine profiles has been implicated in the development of endometriosis. In this study, we analyzed Th17 cells and IL-17A in peritoneal fluid (PF) and endometrial tissues of patients with (n=10) and without (n=26) endometriosis. Our study has shown increased Th17 cell population and IL-17A level in PF with endometriosis patients. To determine the roles of IL-17A and Th17 cells in the development of endometriosis, the effect of IL-17A, major cytokine of Th17, on endometrial cells isolated from endometriotic tissues was examined. Recombinant IL-17A promoted survival of endometrial cells accompanied by increased expression of anti-apoptotic genes, including Bcl-2 and MCL1, and the activation of ERK1/2 signaling. In addition, treatment of IL-17A to endometrial cells inhibited NK cell mediated cytotoxicity and induced HLA-G expression on endometrial cells. IL-17A also promoted migration of endometrial cells. Our data suggest that Th17 cells and IL-17A play critical roles in the development of endometriosis by promoting endometrial cell survival and conferring a resistance to NK cell cytotoxicity through the activation of ERK1/2 signaling. Targeting IL-17A has potential as a new strategy for the treatment of endometriosis.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 2","pages":"e14"},"PeriodicalIF":6.0,"publicationDate":"2023-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/74/b4/in-23-e14.PMC10166657.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9467557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immune NetworkPub Date : 2023-01-27eCollection Date: 2023-04-01DOI: 10.4110/in.2023.23.e12
Min-Hee Kim, Chang-Woo Lee
{"title":"Phosphatase Ssu72 Is Essential for Homeostatic Balance Between CD4<sup>+</sup> T Cell Lineages.","authors":"Min-Hee Kim, Chang-Woo Lee","doi":"10.4110/in.2023.23.e12","DOIUrl":"10.4110/in.2023.23.e12","url":null,"abstract":"<p><p>Ssu72, a dual-specificity protein phosphatase, not only participates in transcription biogenesis, but also affects pathophysiological functions in a tissue-specific manner. Recently, it has been shown that Ssu72 is required for T cell differentiation and function by controlling multiple immune receptor-mediated signals, including TCR and several cytokine receptor signaling pathways. Ssu72 deficiency in T cells is associated with impaired fine-tuning of receptor-mediated signaling and a defect in CD4<sup>+</sup> T cell homeostasis, resulting in immune-mediated diseases. However, the mechanism by which Ssu72 in T cells integrates the pathophysiology of multiple immune-mediated diseases is still poorly elucidated. In this review, we will focus on the immunoregulatory mechanism of Ssu72 phosphatase in CD4<sup>+</sup> T cell differentiation, activation, and phenotypic function. We will also discuss the current understanding of the correlation between Ssu72 in T cells and pathological functions which suggests that Ssu72 might be a therapeutic target in autoimmune disorders and other diseases.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 2","pages":"e12"},"PeriodicalIF":6.0,"publicationDate":"2023-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/05/da/in-23-e12.PMC10166661.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9838434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immune NetworkPub Date : 2023-01-27eCollection Date: 2023-02-01DOI: 10.4110/in.2023.23.e9
Andrea M Amitrano, Minsoo Kim
{"title":"Metabolic Challenges in Anticancer CD8 T Cell Functions.","authors":"Andrea M Amitrano, Minsoo Kim","doi":"10.4110/in.2023.23.e9","DOIUrl":"10.4110/in.2023.23.e9","url":null,"abstract":"<p><p>Cancer immunotherapies continue to face numerous obstacles in the successful treatment of solid malignancies. While immunotherapy has emerged as an extremely effective treatment option for hematologic malignancies, it is largely ineffective against solid tumors due in part to metabolic challenges present in the tumor microenvironment (TME). Tumor-infiltrating CD8<sup>+</sup> T cells face fierce competition with cancer cells for limited nutrients. The strong metabolic suppression in the TME often leads to impaired T-cell recruitment to the tumor site and hyporesponsive effector functions via T-cell exhaustion. Growing evidence suggests that mitochondria play a key role in CD8<sup>+</sup> T-cell activation, migration, effector functions, and persistence in tumors. Therefore, targeting the mitochondrial metabolism of adoptively transferred T cells has the potential to greatly improve the effectiveness of cancer immunotherapies in treating solid malignancies.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 1","pages":"e9"},"PeriodicalIF":4.3,"publicationDate":"2023-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e6/d0/in-23-e9.PMC9995993.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9353922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immune NetworkPub Date : 2022-12-02eCollection Date: 2023-04-01DOI: 10.4110/in.2023.23.e17
Hyeong-A Jo, Seung-Joo Hyun, You-Seok Hyun, Yong-Hun Lee, Sun-Mi Kim, In-Cheol Baek, Hyun-Jung Sohn, Tai-Gyu Kim
{"title":"Comprehensive Analysis of Epstein-Barr Virus LMP2A-Specific CD8<sup>+</sup> and CD4<sup>+</sup> T Cell Responses Restricted to Each HLA Class I and II Allotype Within an Individual.","authors":"Hyeong-A Jo, Seung-Joo Hyun, You-Seok Hyun, Yong-Hun Lee, Sun-Mi Kim, In-Cheol Baek, Hyun-Jung Sohn, Tai-Gyu Kim","doi":"10.4110/in.2023.23.e17","DOIUrl":"10.4110/in.2023.23.e17","url":null,"abstract":"<p><p>Latent membrane protein 2A (LMP2A), a latent Ag commonly expressed in Epstein-Barr virus (EBV)-infected host cells, is a target for adoptive T cell therapy in EBV-associated malignancies. To define whether individual human leukocyte antigen (HLA) allotypes are used preferentially in EBV-specific T lymphocyte responses, LMP2A-specific CD8<sup>+</sup> and CD4<sup>+</sup> T cell responses in 50 healthy donors were analyzed by ELISPOT assay using artificial Ag-presenting cells expressing a single allotype. CD8<sup>+</sup> T cell responses were significantly higher than CD4<sup>+</sup> T cell responses. CD8<sup>+</sup> T cell responses were ranked from highest to lowest in the order HLA-A, HLA-B, and HLA-C loci, and CD4<sup>+</sup> T cell responses were ranked in the order HLA-DR, HLA-DP, and HLA-DQ loci. Among the 32 HLA class I and 56 HLA class II allotypes, 6 HLA-A, 7 HLA-B, 5 HLA-C, 10 HLA-DR, 2 HLA-DQ, and 2 HLA-DP allotypes showed T cell responses higher than 50 spot-forming cells (SFCs)/5×10<sup>5</sup> CD8<sup>+</sup> or CD4<sup>+</sup> T cells. Twenty-nine donors (58%) showed a high T cell response to at least one allotype of HLA class I or class II, and 4 donors (8%) had a high response to both HLA class I and class II allotypes. Interestingly, we observed an inverse correlation between the proportion of LMP2A-specific T cell responses and the frequency of HLA class I and II allotypes. These data demonstrate the allele dominance of LMP2A-specific T cell responses among HLA allotypes and their intra-individual dominance in response to only a few allotypes in an individual, which may provide useful information for genetic, pathogenic, and immunotherapeutic approaches to EBV-associated diseases.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"23 2","pages":"e17"},"PeriodicalIF":6.0,"publicationDate":"2022-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3e/2b/in-23-e17.PMC10166658.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9838437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immune NetworkPub Date : 2022-12-02eCollection Date: 2022-12-01DOI: 10.4110/in.2022.22.e51
Ayorinde Cooley, Kayla J Rayford, Ashutosh Arun, Fernando Villalta, Maria F Lima, Siddharth Pratap, Pius N Nde
{"title":"<i>Trypanosoma cruzi</i> Dysregulates piRNAs Computationally Predicted to Target IL-6 Signaling Molecules During Early Infection of Primary Human Cardiac Fibroblasts.","authors":"Ayorinde Cooley, Kayla J Rayford, Ashutosh Arun, Fernando Villalta, Maria F Lima, Siddharth Pratap, Pius N Nde","doi":"10.4110/in.2022.22.e51","DOIUrl":"10.4110/in.2022.22.e51","url":null,"abstract":"<p><p><i>Trypanosoma cruzi</i>, the etiological agent of Chagas disease, is an intracellular protozoan parasite, which is now present in most industrialized countries. About 40% of <i>T. cruzi</i> infected individuals will develop severe, incurable cardiovascular, gastrointestinal, or neurological disorders. The molecular mechanisms by which <i>T. cruzi</i> induces cardiopathogenesis remain to be determined. Previous studies showed that increased IL-6 expression in <i>T. cruzi</i> patients was associated with disease severity. IL-6 signaling was suggested to induce pro-inflammatory and pro-fibrotic responses, however, the role of this pathway during early infection remains to be elucidated. We reported that <i>T. cruzi</i> can dysregulate the expression of host PIWI-interacting RNAs (piRNAs) during early infection. Here, we aim to evaluate the dysregulation of IL-6 signaling and the piRNAs computationally predicted to target IL-6 molecules during early <i>T. cruzi</i> infection of primary human cardiac fibroblasts (PHCF). Using in silico analysis, we predict that piR_004506, piR_001356, and piR_017716 target <i>IL6</i> and <i>SOCS3</i> genes, respectively. We validated the piRNAs and target gene expression in <i>T. cruzi</i> challenged PHCF. Secreted IL-6, soluble gp-130, and sIL-6R in condition media were measured using a cytokine array and western blot analysis was used to measure pathway activation. We created a network of piRNAs, target genes, and genes within one degree of biological interaction. Our analysis revealed an inverse relationship between piRNA expression and the target transcripts during early infection, denoting the IL-6 pathway targeting piRNAs can be developed as potential therapeutics to mitigate <i>T. cruzi</i> cardiomyopathies.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"22 6","pages":"e51"},"PeriodicalIF":4.3,"publicationDate":"2022-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/2f/f8/in-22-e51.PMC9807959.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10789744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immune NetworkPub Date : 2022-12-01DOI: 10.4110/in.2022.22.e45
Soyoon Sim, Youngwoo Choi, Hae-Sim Park
{"title":"Immunologic Basis of Type 2 Biologics for Severe Asthma.","authors":"Soyoon Sim, Youngwoo Choi, Hae-Sim Park","doi":"10.4110/in.2022.22.e45","DOIUrl":"https://doi.org/10.4110/in.2022.22.e45","url":null,"abstract":"<p><p>Asthma is a chronic airway inflammatory disease characterized by reversible airway obstruction and airway hyperreactivity to various environmental stimuli, leading to recurrent cough, dyspnea, and wheezing episodes. Regarding inflammatory mechanisms, type 2/eosinophilic inflammation along with activated mast cells is the major one; however, diverse mechanisms, including structural cells-derived and non-type 2/neutrophilic inflammations are involved, presenting heterogenous phenotypes. Although most asthmatic patients could be properly controlled by the guided treatment, patients with severe asthma (SA; classified as a treatment-refractory group) suffer from uncontrolled symptoms with frequent asthma exacerbations even on regular anti-inflammatory medications, raising needs for additional controllers, including biologics that target specific molecules found in asthmatic airway, and achieving the precision medicine for asthma. This review summarizes the immunologic basis of airway inflammatory mechanisms and current biologics for SA in order to address unmet needs for future targets.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"22 6","pages":"e45"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/03/c3/in-22-e45.PMC9807964.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10518553","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immune NetworkPub Date : 2022-12-01DOI: 10.4110/in.2022.22.e50
Sujin Lee, Jeong In Yang, Joo Hee Lee, Hyun Woo Lee, Tae Jin Kim
{"title":"Low-Level Expression of CD138 Marks Naturally Arising Anergic B Cells.","authors":"Sujin Lee, Jeong In Yang, Joo Hee Lee, Hyun Woo Lee, Tae Jin Kim","doi":"10.4110/in.2022.22.e50","DOIUrl":"https://doi.org/10.4110/in.2022.22.e50","url":null,"abstract":"<p><p>Autoreactive B cells are not entirely deleted, but some remain as immunocompetent or anergic B cells. Although the persistence of autoreactive B cells as anergic cells has been shown in transgenic mouse models with the expression of B cell receptor (BCR) reactive to engineered self-antigen, the characterization of naturally occurring anergic B cells is important to identify them and understand their contribution to immune regulation or autoimmune diseases. We report here that a low-level expression of CD138 in the splenic B cells marks naturally arising anergic B cells, not plasma cells. The CD138<sup>int</sup> B cells consisted of IgM<sup>low</sup>IgD<sup>high</sup> follicular (FO) B cells and transitional 3 B cells in homeostatic conditions. The CD138<sup>int</sup> FO B cells showed an anergic gene expression profile shared with that of monoclonal anergic B cells expressing engineered BCRs and the gene expression profile was different from those of plasma cells, age-associated B cells, or germinal center B cells. The anergic state of the CD138<sup>int</sup> FO B cells was confirmed by attenuated Ca<sup>2+</sup> response and failure to upregulate CD69 upon BCR engagement with anti-IgM, anti-IgD, anti-Igκ, or anti-IgG. The BCR repertoire of the CD138<sup>int</sup> FO B cells was distinct from that of the CD138<sup>-</sup> FO B cells and included some class-switched B cells with low-level somatic mutations. These findings demonstrate the presence of polyclonal anergic B cells in the normal mice that are characterized by low-level expression of CD138, IgM downregulation, reduced Ca<sup>2+</sup> and CD69 responses upon BCR engagement, and distinct BCR repertoire.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"22 6","pages":"e50"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/25/3f/in-22-e50.PMC9807963.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10524863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immune NetworkPub Date : 2022-12-01DOI: 10.4110/in.2022.22.e47
Geneva Rose Notario, Kihyuck Kwak
{"title":"Increased B Cell Understanding Puts Improved Vaccine Platforms Just Over the Horizon.","authors":"Geneva Rose Notario, Kihyuck Kwak","doi":"10.4110/in.2022.22.e47","DOIUrl":"https://doi.org/10.4110/in.2022.22.e47","url":null,"abstract":"<p><p>In the face of an endlessly expanding repertoire of Ags, vaccines are constantly being tested, each more effective than the last. As viruses and other pathogens evolve to become more infectious, the need for efficient and effective vaccines grows daily, which is especially obvious in an era that is still attempting to remove itself from the clutches of the severe acute respiratory syndrome coronavirus 2, the cause of coronavirus pandemic. To continue evolving alongside these pathogens, it is proving increasingly essential to consider one of the main effector cells of the immune system. As one of the chief orchestrators of the humoral immune response, the B cell and other lymphocytes are essential to not only achieving immunity, but also maintaining it, which is the vital objective of every vaccine.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"22 6","pages":"e47"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/d5/a0/in-22-e47.PMC9807965.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10518551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immune NetworkPub Date : 2022-12-01DOI: 10.4110/in.2022.22.e48
Seung Ho Baek, Hanseul Oh, Bon-Sang Koo, Green Kim, Eun-Ha Hwang, Hoyin Jung, You Jung An, Jae-Hak Park, Jung Joo Hong
{"title":"Cynomolgus Macaque Model for COVID-19 Delta Variant.","authors":"Seung Ho Baek, Hanseul Oh, Bon-Sang Koo, Green Kim, Eun-Ha Hwang, Hoyin Jung, You Jung An, Jae-Hak Park, Jung Joo Hong","doi":"10.4110/in.2022.22.e48","DOIUrl":"https://doi.org/10.4110/in.2022.22.e48","url":null,"abstract":"<p><p>With the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, which are randomly mutated, the dominant strains in regions are changing globally. The development of preclinical animal models is imperative to validate vaccines and therapeutics against SARS-CoV-2 variants. The objective of this study was to develop a non-human primate (NHP) model for SARS-CoV-2 Delta variant infection. Cynomolgus macaques infected with Delta variants showed infectious viruses and viral RNA in the upper (nasal and throat) and lower respiratory (lung) tracts during the acute phase of infection. After 3 days of infection, lesions consistent with diffuse alveolar damage were observed in the lungs. For cellular immune responses, all macaques displayed transient lymphopenia and neutrophilia in the early stages of infection. SARS-CoV-2 Delta variant spike protein-specific IgM, IgG, and IgA levels were significantly increased in the plasma of these animals 14 days after infection. This new NHP Delta variant infection model can be used for comparative analysis of the difference in severity between SARS-CoV-2 variants of concern and may be useful in the efficacy evaluation of vaccines and universal therapeutic drugs for mutations.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"22 6","pages":"e48"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/62/98/in-22-e48.PMC9807958.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10524862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Immune NetworkPub Date : 2022-12-01DOI: 10.4110/in.2022.22.e49
Chuang Sun, Wei Li, Yanhong Li, Jian Chen, Huixian An, Guangwei Zeng, Tingting Wang, Yazhou Guo, Changying Wang
{"title":"MiR-182-5p Mediated by Exosomes Derived From Bone Marrow Mesenchymal Stem Cell Attenuates Inflammatory Responses by Targeting TLR4 in a Mouse Model of Myocardial Infraction.","authors":"Chuang Sun, Wei Li, Yanhong Li, Jian Chen, Huixian An, Guangwei Zeng, Tingting Wang, Yazhou Guo, Changying Wang","doi":"10.4110/in.2022.22.e49","DOIUrl":"https://doi.org/10.4110/in.2022.22.e49","url":null,"abstract":"<p><p>Exosomes derived from mesenchymal stem cells (MSCs) could protect against myocardial infarction (MI). TLR4 is reported to play an important role in MI, while microRNA-182-5p (miR-182-5p) negatively regulates TLR4 expression. Therefore, we hypothesize that MSCs-derived exosomes overexpressing miR-182-5p may have beneficial effects on MI. We generated bone marrow mesenchymal stem cells (BM-MSCs) and overexpressed miR-182-5p in these cells for exosome isolation. H<sub>2</sub>O<sub>2</sub>-stimulated neonatal mouse ventricle myocytes (NMVMs) and MI mouse model were employed, which were subjected to exosome treatment. The expression of inflammatory factors, heart function, and TLR4 signaling pathway activation were monitored. It was found that miR-182-5p decreased TLR4 expression in BM-MSCs and NMVMs. Administration of exosomes overexpressing miR-182-5p to H<sub>2</sub>O<sub>2</sub>-stimulated NMVMs enhanced cell viability and suppressed the expression of inflammatory cytokines. In addition, they promoted heart function, suppressed inflammatory responses, and de-activated TLR4/NF-κB signaling pathway in MI mice. In conclusion, miR-182-5p transferred by the exosomes derived from BM-MSCs protected against MI-induced impairments by targeting TLR4.</p>","PeriodicalId":13307,"journal":{"name":"Immune Network","volume":"22 6","pages":"e49"},"PeriodicalIF":6.0,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/bd/4f/in-22-e49.PMC9807961.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10524861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}