Cellular immunology最新文献

{"title":"Functional responsiveness of in vitro-aged human neutrophils","authors":"J. Morin-Genest,&nbsp;A. Saafane,&nbsp;D. Girard","doi":"10.1016/j.cellimm.2023.104739","DOIUrl":"10.1016/j.cellimm.2023.104739","url":null,"abstract":"<div><p>Elimination of apoptotic neutrophils by macrophages is as a major step for the resolution of inflammation. However, the fate and the cellular functionality of neutrophils aged in the absence of macrophages are not well documented. Herein, freshly isolated human neutrophils were aged for several days <em>in vitro</em> and then stimulated with agonists for determining their cell responsiveness. <em>In vitro</em>-aged neutrophils were still able to generate reactive oxygen species after 48 h, exert phagocytosis after 72 h, and increase their adhesion onto a cell substratum after 48 h. These data demonstrate that a portion of neutrophils cultivated for several days <em>in vitro</em> are still able to exert biological functions. This opens the possibility that, during inflammation, neutrophils may still respond to agonists, a condition that is likely to occur <em>in vivo</em> when they are not efficiently eliminated by efferocytosis.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"390 ","pages":"Article 104739"},"PeriodicalIF":4.3,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9788672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD300f signalling induces inhibitory human monocytes/macrophages","authors":"Sarah I.M. Sutherland ,&nbsp;Xinsheng Ju ,&nbsp;Pablo A. Silveira ,&nbsp;Fiona Kupresanin ,&nbsp;Lisa G. Horvath ,&nbsp;Georgina J. Clark","doi":"10.1016/j.cellimm.2023.104731","DOIUrl":"10.1016/j.cellimm.2023.104731","url":null,"abstract":"<div><p>The CD300 glycoproteins are a family of related leucocyte surface molecules that regulate the immune response via their paired triggering and inhibitory receptors. Here we studied CD300f, an apoptotic cell receptor, and how it modulates the function of human monocytes and macrophages. We showed that CD300f signalling by crosslinking with anti-CD300f mAb (DCR-2) suppressed monocytes causing upregulation of the inhibitory molecule, CD274 (PD-L1) and their inhibition of T cell proliferation. Furthermore, CD300f signalling drove macrophages preferentially towards M2-type with upregulation of CD274, which was further enhanced by IL-4. CD300f signalling activates the PI3K/Akt pathway in monocytes. Inhibition of PI3K/Akt signalling resulting from CD300f crosslinking leads to downregulation of CD274 expression on monocytes. These findings highlight the potential use of CD300f blockade in cancer immune therapy to target immune suppressive macrophages in the tumour microenvironment, a known resistance mechanism to PD-1/PD-L1 checkpoint inhibitors.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"390 ","pages":"Article 104731"},"PeriodicalIF":4.3,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10173238","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-17 receptor C is essential for the pro-inflammatory pathogenicity of granulocyte-macrophage-colony-stimulating factor-producing T helper cells in experimental autoimmune uveitis","authors":"Lina Wu ,&nbsp;Lu Wang ,&nbsp;Xin Chai","doi":"10.1016/j.cellimm.2023.104740","DOIUrl":"10.1016/j.cellimm.2023.104740","url":null,"abstract":"<div><p>Autoimmune uveitis is an inflammatory disorder of the eye triggered by the responses of autoreactive T cells to ocular autoantigens. This study aims to understand the role of granulocyte–macrophage-colony-stimulating factor (GM-CSF)-producing T helper (ThGM) cells in the pathophysiology of mouse experimental autoimmune uveitis (EAU). We established an EAU model by immunizing mice with interphotoreceptor retinoid-binding protein (IRBP) 651–670. Splenic or eye-infiltrating ThGM cells were analyzed and enriched by flow cytometry according to the levels of an array of surface markers, transcription factors, and cytokines. Lentiviral transduction was conducted to silence or overexpress the target gene in differentiated ThGM cells. The adoptive transfer was applied to determine the pathogenicity of ThGM cells <em>in vivo</em>. We found that ThGM cells were present in the spleen and the eye after EAU induction. Both splenic and eye-infiltrating ThGM cells were phenotypically CD4⁺CCR7^-CXCR3^-CCR6^-CCR10^hi. Eye-infiltrating ThGM cells up-regulated interleukin-1β (IL-1β), interleukin-6 (IL-6), and IL-17 receptor C (IL-17RC) relative to splenic ThGM cells. IL-17RC overexpression enabled interleukin-17A (IL-17A)-induced up-regulation of IL-1β and IL-6 production in ThGM cells. Adoptive transfer of IL-17RC overexpressing ThGM cells exacerbated EAU severity, as evidenced by a higher histology score as well as increased pro-inflammatory cytokines and inflammatory cells in the eye. However, IL-17RC-silenced ThGM cells did not impact EAU. Therefore, for the first time, this study unveils the essential pro-inflammatory role of IL-17RC-expressing ThGM cells in EAU pathophysiology. We discovered a novel mechanism underlying the pathophysiology of autoimmune uveitis.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"390 ","pages":"Article 104740"},"PeriodicalIF":4.3,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10156936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mocravimod, a S1P receptor modulator, increases T cell counts in bone marrow biopsies from patients undergoing allogeneic hematopoietic stem cell transplantation","authors":"Simone Dertschnig ,&nbsp;Jakob Passweg ,&nbsp;Christoph Bucher ,&nbsp;Michael Medinger ,&nbsp;Alexandar Tzankov","doi":"10.1016/j.cellimm.2023.104719","DOIUrl":"10.1016/j.cellimm.2023.104719","url":null,"abstract":"<div><p>Graft-versus-leukemia (GvL) effects are critical to prevent relapses after allogeneic hematopoietic cell transplantation (allo-HCT). However, the success of allo-HCT is limited by graft-versus-host disease (GvHD). Both, CD4⁺ and CD8⁺ T cells contribute to GvHD and GvL. The sphingosine-1-phosphate receptor (S1PR) signaling plays a crucial role in lymphocyte trafficking. Mocravimod is an S1PR modulator and its administration leads to blocking lymphocyte egress from lymphoid organs. We hypothesized that this applies to the bone marrow (BM) too, and analyzed BM biopsies from the clinical study with mocravimod (phase I trial in allo-HCT patients; NCT01830010) by immunohistochemical staining for CD3, CD4, CD8, TIA1, FoxP3, PD1, <em>T</em>-Bet, GATA3, and ROR-γt to identify and quantify T cell subsets <em>in situ</em>. Allo-HCT patients without receiving mocravimod were used as controls. BM from 9 patients in the mocravimod group and 10 patients in the control group were examined. CD3⁺ T cells were found to accumulate in the BM of mocravimod-treated patients compared to controls, both on day 30 and 90 post-transplant. The effect was stronger for CD4⁺ T cells, than CD8⁺ T cells, which is in line with data from murine studies showing that CD4⁺ T cells are more sensitive to mocravimod treatment than CD8⁺ T cells. Clinically-relevant acute GvHD events (grade II-IV) were slightly lower, but comparable to controls when mocravimod was administered. Taken together, data are supportive of mocravimod’s mode of action and bring additional evidence of fewer relapses for allo-HCT patients treated with S1PR modulators.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"388 ","pages":"Article 104719"},"PeriodicalIF":4.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10054041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor: Enhancement of macrophage inflammatory responses by CCL2 is correlated with increased miR-9 expression and downregulation of the ERK1/2 phosphatase Dusp6","authors":"Jie Mu,&nbsp;Gang Ma,&nbsp;Rurong Wang","doi":"10.1016/j.cellimm.2017.11.007","DOIUrl":"10.1016/j.cellimm.2017.11.007","url":null,"abstract":"","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"388 ","pages":"Article 103723"},"PeriodicalIF":4.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.cellimm.2017.11.007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9733032","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Paeonol attenuates Substance P-induced urticaria by inhibiting Src kinase phosphorylation in mast cells","authors":"Yuanyuan Ding ,&nbsp;Baowen Dang ,&nbsp;Yonghui Zhang ,&nbsp;Shiting Hu ,&nbsp;Yuejin Wang ,&nbsp;Chenrui Zhao ,&nbsp;Tao Zhang ,&nbsp;Zijun Gao","doi":"10.1016/j.cellimm.2023.104728","DOIUrl":"10.1016/j.cellimm.2023.104728","url":null,"abstract":"<div><h3>Background</h3><p>Treatment of chronic urticaria is challenging, the discovery of effective therapeutic drugs is urgently in demand.</p></div><div><h3>Purpose</h3><p>To study the effect and mechanism of Paeonol targeting mast cells and its therapeutic effect on chronic urticaria.</p><p>Study design: We developed a chronic urticaria model <em>in vivo</em> and mast cell model in vitro examined the effect of Paeonol in the treatment of chronic urticaria and its mechanism of action in mast cells.</p></div><div><h3>Method</h3><p>The anti-anaphylactoid effect of Paeonol was evaluated in PCA and systemic anaphylaxis models. The treatment role of Paeonol was studied in urticaria model. The release of cytokines and chemokines was measured using enzyme immunoassay kits. Western blot analysis was conducted to investigate phosphorylation of Src, PI3K, and PLC. In vitro kinase assays were conducted to investigate the kinase activity of Lyn, PLC, PI3K and Src.</p></div><div><h3>Results</h3><p>In our study, Paeonol was able to attenuate evans blue leakage, serum histamine and chemokine release in a passive skin allergic reaction model. Simultaneously, Paeonol inhibited vasodilation and mast cell degranulation in C57BL/6 mice. Further research found that Paeonol alleviated symptoms such as erythema and rash in the Substance P-induced urticaria model, this is accompanied by inhibiting the release of related inflammatory factors. Validation experiments on mast cells in vitro found that Paeonol inhibited the activation of Src-PI3K/Lyn-PLC-NF-κB signaling pathway by crosslinking with Src kinase. Moreover, calcium influx, mast cell degranulation, cytokines generation and chemotaxis were reduced in LAD2 cells. Molecular docking experiments revealed that Paeonol is a specific antagonist targeting Src kinase in the treatment of skin diseases such as urticaria.</p></div><div><h3>Conclusion</h3><p>Paeonol, a herb-derived phenolic compound, can provide drug candidate for developing new drug in treatment of skin disease such as urticaria.</p></div><div><h3>Significance statement</h3><p>In this study, we primarily examined the effect of Paeonol in the treatment of chronic urticaria and its mechanism of action in mast cells. Interestingly, Paeonol was found to regulate Src kinase activity downstream of MRGPRX2 triggered signaling cascade in mast cells. Therefore, this plant-derived phenolic compound may provide a therapeutic option for the treatment of chronic urticaria.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"388 ","pages":"Article 104728"},"PeriodicalIF":4.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9680460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Downregulation of HHLA2 inhibits ovarian cancer progression via the NF-κB signaling pathway and suppresses the expression of CA9","authors":"Yuanyuan Fu ,&nbsp;Panpan Zheng ,&nbsp;Xiao Zheng ,&nbsp;Lujun Chen ,&nbsp;Caixia Kong ,&nbsp;Wenzhi Liu ,&nbsp;Shuping Li ,&nbsp;Jingting Jiang","doi":"10.1016/j.cellimm.2023.104730","DOIUrl":"10.1016/j.cellimm.2023.104730","url":null,"abstract":"<div><p>HHLA2 has been recently demonstrated to play multifaceted roles in several types of cancers. However, its underlying mechanism in the progression of human ovarian cancer (OC) remains largely unexplored. In the present study, we aimed to determine whether downregulation of HHLA2 inhibited malignant phenotypes of human OC cells and explore its specific mechanism. Our results revealed that downregulation of HHLA2 by transfection with a lentiviral vector significantly suppressed the viability, invasion, and migration of OC cells. Interaction study showed that downregulation of HHLA2 in OC cells reduced the expression of CA9 and increased the expressions of p-IKKβ and p-RelA. Conversely, the viability, invasion, and migration of HHLA2-depleted OC cells were increased when CA9 was upregulated. In vivo, we found that downregulation of HHLA2 significantly inhibited tumor growth, which was reversed by CA9 overexpression. In addition, downregulation of HHLA2 inhibited the OC progression via activating the NF-κB signaling pathway and decreasing the expression of CA9. Collectively, our data suggested a link between HHLA2 and NF-κB axis in the pathogenesis of OC, and these findings might provide valuable insights into the development of novel potential therapeutic targets for OC.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"388 ","pages":"Article 104730"},"PeriodicalIF":4.3,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10054048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IFN-β activates cytotoxic function of human natural killer cells toward IL-27 and poly(I:C) stimulated PC3 and DU145 cells","authors":"Olena Kourko,&nbsp;Lindsey G. Hawke,&nbsp;Mark L. Ormiston,&nbsp;Katrina Gee","doi":"10.1016/j.cellimm.2023.104718","DOIUrl":"10.1016/j.cellimm.2023.104718","url":null,"abstract":"<div><p>Natural killer (NK) cell phenotype and function are altered in patients with prostate cancer, and increased NK cell activity is associated with a better prognosis in patients with disease. For patients with advanced stage prostate cancer, immunotherapies are a promising approach when standard treatment options have been exhausted. With the rapid emergence of NK cell-based therapies, it is important to understand the mechanisms by which NK cells can be triggered to kill cancer cells that have developed immune-evasive strategies. Altering the cytokine profiles of advanced prostate cancer cells may be an area to explore when considering ways in which NK cell activation can be modulated. We have previously demonstrated that combining the cytokine, IL-27, with TLR3 agonist, poly(I:C), changes cytokine secretion in the advanced prostate cancer models, PC3 and DU145 cells. Herein, we extend our previous work to study the effect of primary human NK cells on prostate cancer cell death in an <em>in vitro</em> co-culture model. Stimulating PC3 and DU145 cells with IL-27 and poly(I:C) induced IFN-β secretion, which was required for activation of primary human NK cells to kill these stimulated prostate cancer cells. PC3 cells were more sensitized to NK cell-mediated killing when compared to DU145 cells, which was attributed to differential levels of IFN-β produced in response to stimulation with IL-27 and poly(I:C). IFN-β increased granzyme B secretion and membrane-bound TRAIL expression by co-cultured NK cells. We further demonstrated that these NK cells killed PC3 cells in a partially TRAIL-dependent manner. This work provides mechanistic insight into how the cytotoxic function of NK cells can be improved to target cancer cells.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"387 ","pages":"Article 104718"},"PeriodicalIF":4.3,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9733566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of the different subpeptidomes presented by the HLA class I molecules of the B7 supertype","authors":"Adrián Tirado-Herranz ,&nbsp;Pablo Guasp ,&nbsp;Alba Pastor-Moreno ,&nbsp;María Area-Navarro ,&nbsp;Iñaki Alvarez","doi":"10.1016/j.cellimm.2023.104707","DOIUrl":"10.1016/j.cellimm.2023.104707","url":null,"abstract":"<div><p>MHC-I molecules of the HLA-B7 supertype preferentially bind peptides with proline at position 2. HLA-B*51:01 and B*51:08 present two predominant subpeptidomes, one with Pro2 and hydrophobic residues at <em>P</em>1, and another with Ala2 and Asp enriched at position 1. Here, we present a <em>meta</em>-analysis of the peptidomes presented by molecules of the B7 supertype to investigate the presence of subpeptidomes across different allotypes. Several allotypes presented subpeptidomes differing in the presence of Pro or another residue at <em>P</em>2. The Ala2 subpeptidomes preferred Asp1 except in HLA-B*54:01, where ligands with Ala2 contained Glu1. Sequence alignment and the analysis of crystal structures allowed us to propose positions 45 and 67 of the MHC heavy chain as relevant for the presence of subpeptidomes. Deciphering the principles behind the presence of subpeptidomes could improve our understanding of antigen presentation in other MHC-I molecules.</p><p>Running title: HLA-B7 supertype subpeptidomes.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"387 ","pages":"Article 104707"},"PeriodicalIF":4.3,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10337693/pdf/nihms-1910168.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9828533","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}

{"title":"Aberrant pro-inflammatory responses of CD20+ T cells in experimental arthritis","authors":"Piaopiao Pan ,&nbsp;Miguel A. Pineda ,&nbsp;Yilin Wang ,&nbsp;Aneesah Khan ,&nbsp;Mukanthu H. Nyirenda","doi":"10.1016/j.cellimm.2023.104717","DOIUrl":"https://doi.org/10.1016/j.cellimm.2023.104717","url":null,"abstract":"<div><p>CD20⁺ T cells comprise a highly inflammatory subset implicated in autoimmunity, including rheumatoid arthritis (RA). We sought to characterize the CD20⁺ T cell subset in the murine collagen-induced arthritis (CIA) model of RA and investigate the phenotype and functional relevance of CD3⁺CD20⁺ T cells in the lymph nodes and arthritic joints using flow cytometry and immunohistochemistry. We demonstrate that CD3⁺CD4⁺CD20⁺ and CD3⁺CD8⁺CD20⁺ T cells are expanded in the draining lymph nodes of CIA mice, produce increased levels of pro-inflammatory cytokines and are less susceptible to regulation by regulatory T cells. Notably, CD3⁺CD4⁺CD20⁺ and CD3⁺CD8⁺CD20⁺ T cells are enriched with CXCR5⁺PD-1⁺ T follicular helper cells and CXCR5^-PD-1⁺ peripheral T helper cells, subsets of T cells implicated in promoting B-cell responses and antibody production within pathologically inflamed non-lymphoid tissues in RA. Our findings suggest CD20⁺ T cells are associated with inflammatory responses and may exacerbate pathology by promoting inflammatory B-cell responses.</p></div>","PeriodicalId":9795,"journal":{"name":"Cellular immunology","volume":"387 ","pages":"Article 104717"},"PeriodicalIF":4.3,"publicationDate":"2023-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49813269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}