{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Verghese DA"],"funding":["NIDDK NIH HHS","NIAID NIH HHS","Leukemia Society of America","NCI NIH HHS","National Institutes of Health","NIH HHS"],"pagination":["124646"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6338317"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["3(24)"],"pubmed_abstract":["CD4+ follicular helper T (Tfh) cells are specialized providers of T cell help to B cells and can function as pathogenic mediators of murine antibody-dependent chronic graft-versus-host disease (GvHD). Using a parent→F1 model of lupus-like chronic GvHD, in which Tfh cell and germinal center (GC) B cell differentiation occurs over 14 days, we demonstrate that absence of CD4+ T cell-expressed C5a receptor 1 (C5ar1) or pharmacological C5aR1 blockade abrogated generation/expansion of Tfh cells, GC B cells, and autoantibodies. In a Tfh cell-dependent model of chronic GvHD manifested by bronchiolitis obliterans syndrome (BOS), C5aR1 antagonism initiated in mice with established disease ameliorated BOS and abolished the associated differentiation of Tfh and GC B cells. Guided by RNA-sequencing data, mechanistic studies performed using murine and human T cells showed that C5aR1 signaling amplifies IL-6-dependent expression of the transcription factor c-MAF and the cytokine IL-21 via phosphorylating phosphokinase B (AKT) and activating the mammalian target of rapamycin (mTOR). In addition to linking C5aR1-initiated signaling to Tfh cell differentiation, our findings suggest that C5aR1 may be a useful therapeutic target for prevention and/or treatment of individuals with Tfh cell-dependent diseases, including those chronic GvHD patients who have anti-host reactive antibodies."],"journal":["JCI insight"],"pubmed_title":["C5aR1 regulates T follicular helper differentiation and chronic graft-versus-host disease bronchiolitis obliterans."],"pmcid":["PMC6338317"],"funding_grant_id":["P01 CA142106","translational research grant 6458","K08 AI135101","R01 AI071185","T32 AI078892","P01 AI056299","S10 OD018522","R01 AI071185,P01 CA142106,P01 AI 056299,R01 HL11879,T32 DK007757,T32 AI078892.","T32 DK007757"],"pubmed_authors":["Yi Z","Paz K","Hu Y","Woodruff TM","Heeger PS","Blazar BR","Chun N","Verghese DA","Zhang W","Fribourg M","Flynn R","Du J","Xiong H"],"additional_accession":[]},"is_claimable":false,"name":"C5aR1 regulates T follicular helper differentiation and chronic graft-versus-host disease bronchiolitis obliterans.","description":"CD4+ follicular helper T (Tfh) cells are specialized providers of T cell help to B cells and can function as pathogenic mediators of murine antibody-dependent chronic graft-versus-host disease (GvHD). Using a parent→F1 model of lupus-like chronic GvHD, in which Tfh cell and germinal center (GC) B cell differentiation occurs over 14 days, we demonstrate that absence of CD4+ T cell-expressed C5a receptor 1 (C5ar1) or pharmacological C5aR1 blockade abrogated generation/expansion of Tfh cells, GC B cells, and autoantibodies. In a Tfh cell-dependent model of chronic GvHD manifested by bronchiolitis obliterans syndrome (BOS), C5aR1 antagonism initiated in mice with established disease ameliorated BOS and abolished the associated differentiation of Tfh and GC B cells. Guided by RNA-sequencing data, mechanistic studies performed using murine and human T cells showed that C5aR1 signaling amplifies IL-6-dependent expression of the transcription factor c-MAF and the cytokine IL-21 via phosphorylating phosphokinase B (AKT) and activating the mammalian target of rapamycin (mTOR). In addition to linking C5aR1-initiated signaling to Tfh cell differentiation, our findings suggest that C5aR1 may be a useful therapeutic target for prevention and/or treatment of individuals with Tfh cell-dependent diseases, including those chronic GvHD patients who have anti-host reactive antibodies.","dates":{"release":"2018-01-01T00:00:00Z","publication":"2018 Dec","modification":"2026-05-03T00:46:20.606Z","creation":"2026-04-07T18:43:23.279Z"},"accession":"S-EPMC6338317","cross_references":{"pubmed":["30568034"],"doi":["10.1172/jci.insight.124646"]}}