Molecular immunology最新文献

{"title":"Corrigendum to “Inhibition of PIM1 kinase attenuates bleomycin-induced pulmonary fibrosis in mice by modulating the ZEB1/E-cadherin pathway in alveolar epithelial cells” [Mol. Immunol. 125 (2020) 15–22]","authors":"Xinyi Zhang , Yun Zou , Yuqi Liu , Yumeng Cao , Jiali Zhu , Jianhai Zhang , Xia Chen , Rui Zhang , Jinbao Li","doi":"10.1016/j.molimm.2024.04.014","DOIUrl":"10.1016/j.molimm.2024.04.014","url":null,"abstract":"","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"171 ","pages":"Pages 115-116"},"PeriodicalIF":3.6,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0161589024000841/pdfft?md5=ade6c7d72f681e6a9e39d406321da602&pid=1-s2.0-S0161589024000841-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141262448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rosmarinic acid activates the Ras/Raf/MEK/ERK signaling pathway to regulate CD8+ T cells and autophagy to clear Chlamydia trachomatis in reproductive tract-infected mice","authors":"Zhou Si Yun ,&nbsp;Song Zhihua ,&nbsp;Tian Xuelian ,&nbsp;Xia Min ,&nbsp;Hu Rongjing ,&nbsp;Luo Mei","doi":"10.1016/j.molimm.2024.05.007","DOIUrl":"10.1016/j.molimm.2024.05.007","url":null,"abstract":"<div><p><em>Chlamydia trachomatis</em> (CT) is the leading cause of bacterial sexually transmitted diseases worldwide, which can cause diseases such as pelvic inflammatory disease, and cervical and fallopian tube inflammation, and poses a threat to human health. Rosmarinic acid (RosA) is an active ingredient of natural products with anti-inflammatory and immunomodulatory effects. This study aimed to investigate the role of RosA in inhibiting autophagy-regulated immune cells-CD8+ T cells via the Ras/Raf/MEK/ERK signaling pathway in a CT-infected mouse model. Mice were inoculated with CT infection solution vaginally, and the mechanistic basis of RosA treatment was established using H&amp;E staining, flow cytometry, immunofluorescence, transmission electron microscopy, and western blot. The key factors involved in RosA treatment were further validated using the MEK inhibitor cobimetinib. Experimental results showed that both RosA and the reference drug azithromycin could attenuate the pathological damage to the endometrium caused by CT infection; flow cytometry showed that peripheral blood CD8+ T cells increased after CT infection and decreased after treatment with RosA and the positive drug azithromycin (positive control); immunofluorescence showed that endometrial CD8 and LC3 increased after CT infection and decreased after RosA and positive drug treatment; the results of transmission electron microscopy showed that RosA and the positive drug azithromycin inhibited the accumulation of autophagosomes; western bolt experiments confirmed the activation of autophagy proteins LC3Ⅱ/Ⅰ, ATG5, Beclin-1, and p62 after CT infection, as well as the inhibition of Ras/Raf/MEK/ERK signaling. RosA and azithromycin inhibition of autophagy proteins activates Ras/Raf/MEK/ERK signaling. In addition, the MEK inhibitor cobimetinib attenuated RosA's protective effect on endometrium by further activating CD8+ T cells on a CT-induced basis, while transmission electron microscopy, immunofluorescence, and western blots showed that cobimetinib blocked ERK signals activation and further induced phagocytosis on a CT-induced basis. These data indicated that RosA can activate the Ras/Raf/MEK/ERK signaling pathway to inhibit autophagy, and RosA could also regulate the activation of immune cells-CD8+T cells to protect the reproductive tract of CT-infected mice.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"171 ","pages":"Pages 105-114"},"PeriodicalIF":3.6,"publicationDate":"2024-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating the protective effects of Astragalus polysaccharides on cyclophosphamide-induced bone marrow suppression in mice and bone mesenchymal stem cells","authors":"Wen Wang ,&nbsp;Kangle Zhang ,&nbsp;Lingling Dai ,&nbsp;Aihua Hou ,&nbsp;Peng Meng ,&nbsp;Jipeng Ma","doi":"10.1016/j.molimm.2024.05.008","DOIUrl":"10.1016/j.molimm.2024.05.008","url":null,"abstract":"<div><h3>Background</h3><p>This study determines the role and mechanism of APS in cyclophosphamide-induced myelosuppression in mice and bone mesenchymal stem cells (BMSCs) cell model.</p></div><div><h3>Methods</h3><p>Cy-induced myelosuppression mice and BMSCs cell model were established. Fifty C57BL/6 mice (weighing 20 ± 2 g) were randomly divided into five groups. Femur and tibia samples, bone marrow samples, and blood samples were collected 3 days after the last injection of Cy. Histopathology changes and cell apoptosis were detected. Cell viability, apoptosis, cycle distribution, reactive oxygen species activity, osteogenesis ability, and protein levels were detected. γ-H2AX and senescence-associated β-galactosidase activity expression was detected by immunofluorescence. Cy-induced senescence and Wnt/β-catenin related protein levels were detected using western blotting.</p></div><div><h3>Results</h3><p>The results showed that APS effectively induced Cy-induced histological injury and cell apoptosis rate. After treated with APS, ROS and ALP levels were significantly increased. In BMSCs, cell viability, apoptosis, and cell cycle distribution were also influenced by APS treatment. Compared with the control group, cell viability was significantly increased, the cell apoptosis rate was decreased while the number of cells remained in the G0-G1 phase was increased. Meanwhile, ROS levels were significantly increased in APS group. Cell senescence and Wnt/β-catenin related protein (γ-H2AX, SA-β-gal, p21, p16, p-β-catenin/ β-catenin, c-Myc, and AXIN2) levels were also altered both <em>in vivo</em> and <em>in vitro</em>. Interestingly, the effects of APS were reversed by BML-284.</p></div><div><h3>Conclusion</h3><p>Our results indicate that APS protected Cy-induced myelosuppression through the Wnt/β-catenin pathway and APS is a potential therapeutic drug for Cy-induced myelosuppression.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"171 ","pages":"Pages 93-104"},"PeriodicalIF":3.6,"publicationDate":"2024-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141162103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of HPV-E7 specific TCRs for tumor immunotherapy","authors":"Xiaowen Li ,&nbsp;Wenling Wang ,&nbsp;Jie Wang ,&nbsp;Min Jiang ,&nbsp;Juanhua He ,&nbsp;Shuguang Tan","doi":"10.1016/j.molimm.2024.05.006","DOIUrl":"https://doi.org/10.1016/j.molimm.2024.05.006","url":null,"abstract":"<div><p>The oncogenic protein E7 of the Human Papillomavirus (HPV) is constitutionally expressed in HPV-associated tumors and has the potential to be targeted in T cell receptor (TCR)-based immunotherapy. Adoptive transfer of TCR-engineered T (TCR-T) cells has shown promise as a therapeutic approach for HPV-induced tumors. This study aimed to identify HPV-E7 specific TCRs from HLA-A11:01 transgenic mice through single-cell sorting and sequencing facilitated by E7_89–97/HLA-A11:01 tetramer. Two dominant TCRs were identified, which exhibited specific binding to E7_89–97 presented in the context of HLA-A*11:01. TCR-T cells were prepared by infecting primary T cells with lentiviruses containing the TCR genes, and the two TCRs demonstrated substantial responsiveness and showed CD8+ dependent cytokine secretion characteristics. Further analyses of the cytokine profiles revealed that the two TCRs were capable of exerting polyfunctional responses upon specific stimulation. These findings suggest that the two TCRs represent promising candidates for the development of future therapeutic drugs targeting HPV-E7 in the context of HLA-A*11:01 for tumor immunotherapy.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"171 ","pages":"Pages 56-65"},"PeriodicalIF":3.6,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complement decay-accelerating factor inhibits inflammation-induced myopia development","authors":"Yung-Lan Chou ,&nbsp;Yu-An Hsu ,&nbsp;Chi-Fong Lin ,&nbsp;Chih-Sheng Chen ,&nbsp;Peng-Tai Tien ,&nbsp;Yao-Chien Wang ,&nbsp;Ching-Yao Chang ,&nbsp;En-Shyh Lin ,&nbsp;Jamie Jiin-Yi Chen ,&nbsp;Ming-Yen Wu ,&nbsp;Chun-Yu Chuang ,&nbsp;Hui-Ju Lin ,&nbsp;Lei Wan","doi":"10.1016/j.molimm.2024.05.005","DOIUrl":"https://doi.org/10.1016/j.molimm.2024.05.005","url":null,"abstract":"<div><p>Myopia is regarded as a worldwide epidemic ocular disease, has been proved related to inflammation. CD55, also known as decay-accelerating factor (DAF) can modulate the activation of complement through inhibiting the formation of complement 3 convertase and its dysregulation is involved in various inflammatory diseases. To investigate the association between CD55 and myopia, and to test whether CD55 can inhibit myopia development by suppressing inflammation in the eye, we use three different animal models including monocular form-deprivation myopia, myopia induced by TNF-α administration and allergic conjunctivitis animal model to reveal the CD55 in myopia development. The tears of thirty-eight participants with different spherical equivalents were collected and CD55 in the tears were also analyzed. Complement 3 and complement 5 levels increased while CD55 levels decreased in allergic conjunctivitis and myopic eyes. After anti-inflammatory drugs administration, CD55 expression was increased in monocular form-deprivation myopia model. We also found inflammatory cytokines TGF-β, IL-6, TNF-α, and IL-1β may enhance complement 3 and complement 5 activation while CD55 level was suppressed contrary. Moreover, lower CD55 levels were found in the tears of patients with myopia with decreased diopter values. Finally, CD55-Fc administration on the eyelids can inhibit the elongation of axial length and change of refractive error. CD55-Fc application also suppress myopia development subsequent to complement 3 and complement 5 reduction and can lower myopia-specific (MMP-2 and TGF-β) cytokine expression in TNF-α induced myopia animal model. This suggests that CD55 can inhibit myopia development by suppression of complement activation and eventual down-regulation of inflammation.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"171 ","pages":"Pages 47-55"},"PeriodicalIF":3.6,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141090070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative analysis of systemic lupus erythematosus biomarkers: Role of fecal hsa-mir-223–3p and gut microbiota in transkingdom dynamics","authors":"Sofía Quesada ,&nbsp;Ayelén Daiana Rosso ,&nbsp;Florencia Mascardi ,&nbsp;Valeria Soler-Rivero ,&nbsp;Pablo Aguilera ,&nbsp;Sebastian Nicolas Mascuka ,&nbsp;Andrea Boiro ,&nbsp;Evangelina Arenielo ,&nbsp;Gustavo Vijoditz ,&nbsp;Leila Romina Ferreyra-Mufarregue ,&nbsp;Marina Flavia Caputo ,&nbsp;María Cecilia Cimolai ,&nbsp;Federico Coluccio Leskow ,&nbsp;Alberto Penas-Steinhardt ,&nbsp;Fiorella Sabrina Belforte","doi":"10.1016/j.molimm.2024.05.004","DOIUrl":"https://doi.org/10.1016/j.molimm.2024.05.004","url":null,"abstract":"<div><p>Systemic lupus erythematosus (SLE) involves a florid set of clinical manifestations whose autoreactive origin is characterized by an overactivation of the immune system and the production of a large number of autoantibodies. Because it is a complex pathology with an inflammatory component, its pathogenesis is not yet fully understood, assuming both genetic and environmental predisposing factors. Currently, it is known that the role of the human microbiome is crucial in maintaining the transkingdom balance between commensal microorganisms and the immune system. In the present work we study the intestinal microbiota of Argentine patients with different stages of SLE receiving or not different treatments. Microbiota composition and fecal miRNAs were assessed by 16 S sequencing and qPCR. hsa-miR-223–3p, a miRNA involved in several inflammation regulation pathways, was found underexpressed in SLE patients without immunosuppressive treatment. In terms of microbiota there were clear differences in population structure (Weighted and Unweighted Unifrac distances, p-value &lt;0.05) and core microbiome between cases and controls. In addition, <em>Collinsella, Bifidobacterium, Streptococcus</em> genera and aromatics degradation metabolisms were overrepresented in the SLE group. Medical treatment was also determinant as several microbial metabolic pathways were influenced by immunosuppressive therapy. Particularly, allantoin degradation metabolism was differentially expressed in the group of patients receiving immunosuppressants. Finally, we performed a logistic regression model (LASSO: least absolute shrinkage and selection operator) considering the expression levels of the fecal hsa-miR223–3p; the core microbiota; the differentially abundant bacterial taxa and the differentially abundant metabolic pathways (p&lt;0.05). The model predicted that SLE patients could be associated with greater relative abundance of the formaldehyde oxidation pathway (RUMP_PWY). On the contrary, the preponderance of the ketodeoxyoctonate (Kdo) biosynthesis and activation route (PWY_1269) and the genera Lachnospiraceae_UCG_004, Lachnospira, Victivallis and UCG_003 (genus belonging to the family Oscillospiraceae of the class Clostridia) were associated with a control phenotype. Overall, the present work could contribute to the development of integral diagnostic tools for the comprehensive phenotyping of patients with SLE. In this sense, studying the commensal microbial profile and possible pathobionts associated with SLE in our population proposes more effective and precise strategies to explore possible treatments based on the microbiota of SLE patients.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"171 ","pages":"Pages 77-92"},"PeriodicalIF":3.6,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141089911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IL-17 in type II diabetes mellitus (T2DM) immunopathogenesis and complications; molecular approaches","authors":"Reza Elahi ,&nbsp;Mahdis Nazari ,&nbsp;Vahid Mohammadi ,&nbsp;Kimia Esmaeilzadeh ,&nbsp;Abdolreza Esmaeilzadeh","doi":"10.1016/j.molimm.2024.03.009","DOIUrl":"https://doi.org/10.1016/j.molimm.2024.03.009","url":null,"abstract":"<div><p>Chronic inflammation has long been considered the characteristic feature of type II diabetes mellitus (T2DM) Immunopathogenesis. Pro-inflammatory cytokines are considered the central drivers of the inflammatory cascade leading to β-cell dysfunction and insulin resistance (IR), two major pathologic events contributing to T2DM. Analyzing the cytokine profile of T2DM patients has also introduced interleukin-17 (IL-17) as an upstream regulator of inflammation, regarding its role in inducing the nuclear factor-kappa B (NF-κB) pathway. In diabetic tissues, IL-17 induces the expression of inflammatory cytokines and chemokines. Hence, IL-17 can deteriorate insulin signaling and β-cell function by activating the JNK pathway and inducing infiltration of neutrophils into pancreatic islets, respectively. Additionally, higher levels of IL-17 expression in patients with diabetic complications compared to non-complicated individuals have also proposed a role for IL-17 in T2DM complications. Here, we highlight the role of IL-17 in the Immunopathogenesis of T2DM and corresponding pathways, recent advances in preclinical and clinical studies targeting IL-17 in T2DM, and corresponding challenges and possible solutions.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"171 ","pages":"Pages 66-76"},"PeriodicalIF":3.6,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141090069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The roles of B cells in cardiovascular diseases","authors":"Jian Ma ,&nbsp;Xiaotong Wang ,&nbsp;Yuewang Jia ,&nbsp;Fangyan Tan ,&nbsp;Xin Yuan ,&nbsp;Jianlin Du","doi":"10.1016/j.molimm.2024.05.002","DOIUrl":"10.1016/j.molimm.2024.05.002","url":null,"abstract":"<div><p>Damage to the heart can start the repair process and cause cardiac remodeling. B cells play an important role in this process. B cells are recruited to the injured place and activate cardiac remodeling through secreting antibodies and cytokines. Different types of B cells showed specific functions in the heart. Among all types of B cells, heart-associated B cells play a vital role in the heart by secreting TGFβ1. B cells participate in the activation of fibroblasts and promote cardiac fibrosis. Four subtypes of B cells in the heart revealed the relationship between the B cells' heterogeneity and cardiac remodeling. Many cardiovascular diseases like atherosclerosis, heart failure (HF), hypertension, myocardial infarction (MI), and dilated cardiomyopathy (DCM) are related to B cells. The primary mechanisms of these B cell-related activities will be discussed in this review, which may also suggest potential novel therapeutic targets.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"171 ","pages":"Pages 36-46"},"PeriodicalIF":3.6,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IFN-α affects Th17/Treg cell balance through c-Maf and associated with the progression of EBV- SLE","authors":"Yue Zhang ,&nbsp;Jiachao Wang ,&nbsp;Yaqi Fang ,&nbsp;Wenzhang Liang ,&nbsp;Lingyan Lei ,&nbsp;Junhai Wang ,&nbsp;Xue Gao ,&nbsp;Cuiqing Ma ,&nbsp;Miao Li ,&nbsp;Huifang Guo ,&nbsp;Lin Wei","doi":"10.1016/j.molimm.2024.05.003","DOIUrl":"10.1016/j.molimm.2024.05.003","url":null,"abstract":"<div><h3>Objectives</h3><p>Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease, of which the pathogens is remains obscure. Viral infection, particularly Epstein Barr viru (EBV) infection, has been considered a common pathogenic factor. This study suggests that c-Maf may be an important target in T cell differentiation during SLE progression, providing a potentially new perspective on the role of viral infection in the pathogenesis of autoimmune diseases.</p></div><div><h3>Methods</h3><p>Cytokines of EBV-infected SLE patients were measured by ELISA and assessed in conjunction with their clinical data. IFN-α, c-Maf, and the differentiation of Th17/Treg cells in SLE patients and MRL/LPR mice were analyzed using FCM, WB, RT-PCR, etc. Following the infection of cells and mice with EBV or viral mimic poly (dA:dT), the changes of the aforementioned indicators were investigated. The relationship among IFN-α, STAT3, c-Maf and Th17 cells was determined by si-RNA technique.</p></div><div><h3>Results</h3><p>Many SLE patients are found to be complicated by viral infections; Further, studies have demonstrated that viral infection, especially EBV, is involved in SLE development. This study showed that viral infections might promote IFN-α secretion, inhibit c-Maf expression by activating STAT3, increase Th17 cell differentiation, and lead to the immune imbalance of Th17/Treg cells, thus playing a role in the onset and progression of SLE.</p></div><div><h3>Conclusion</h3><p>This study demonstrates that EBV infections may contribute to SLE development by activating STAT3 through IFN-α, inhibiting c-Maf, and causing Th17/Treg immune imbalance. Our work provided a new insight into the pathogenesis and treatment of SLE.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"171 ","pages":"Pages 22-35"},"PeriodicalIF":3.6,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0161589024000889/pdfft?md5=e4aceaffbe1c2c57a17ca17ebd5d272c&pid=1-s2.0-S0161589024000889-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140945530","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MXRA7 is involved in monocyte-to-macrophage differentiation","authors":"Zhenjiang Sun ,&nbsp;Peng Ke ,&nbsp;Ying Shen ,&nbsp;Kunpeng Ma ,&nbsp;Benfang Wang ,&nbsp;Dandan Lin ,&nbsp;Yiqiang Wang","doi":"10.1016/j.molimm.2024.05.001","DOIUrl":"https://doi.org/10.1016/j.molimm.2024.05.001","url":null,"abstract":"<div><p>Macrophages are critical in mediating immune and inflammatory responses, while monocyte-to-macrophage differentiation is one of the main macrophage resources that involves various matrix proteins. Matrix remodeling associated 7 (MXRA7) was recently discovered to affect a variety of physiological and pathological processes related to matrix biology. In the present study, we investigated the role of MXRA7 in monocyte-to-macrophage differentiation in vitro. We found that knockdown of MXRA7 inhibited the proliferation of THP-1 human monocytic cells. Knockdown of MXRA7 increased the adhesion ability of THP-1 cells through upregulation the expression of adhesion molecules VCAM-1 and ICAM1. Knockdown of MXRA7 alone could promoted the differentiation of THP-1 cells to macrophages. Furthermore, the MXRA7-knockdown THP-1 cells produced a more significant upregulation pattern with M1-type cytokines (TNF-α, IL-1β and IL-6) than with those M2-type molecules (TGF-β1 and IL-1RA) upon PMA stimulation, indicating that knockdown of MXRA7 facilitated THP-1 cells differentiation toward M1 macrophages. RNA sequencing analysis revealed the potential biological roles of MXRA7 in cell adhesion, macrophage and monocyte differentiation. Moreover, MXRA7 knockdown promoted the expression of NF-κB p52/p100, while PMA stimulation could increase the expression of NF-κB p52/p100 and activating MAPK signaling pathways in MXRA7 knockdown cells. In conclusion, MXRA7 affected the differentiation of THP-1 cells toward macrophages possibly through NF-κB signaling pathways.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":"171 ","pages":"Pages 12-21"},"PeriodicalIF":3.6,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140906768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}