T-Cell Immune Imbalance in Rheumatoid Arthritis Is Associated with Alterations in NK Cells and NK-Like T Cells Expressing CD38 |
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Authors: | Hongxing Wang Kehua Fang Weining Yan Xiaotian Chang |
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Institution: | aMedical Research Center of The Affiliated Hospital of Qingdao University, Qingdao, China;bClinical Laboratory of Qilu Hospital, Shandong University, Jinan, China;cClinical Laboratory of The Affiliated Hospital of Qingdao University, Qingdao, China;dJoint Surgery Department of The Affiliated Hospital of Qingdao University, Qingdao, China;eQingdao Engineering Technology Center for Major Disease Marker, Qingdao, China |
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Abstract: | BackgroundCD38+ NK (CD3− CD16+ CD38+ CD56+) cells were increased in rheumatoid arthritis (RA), which suppressed Treg cell differentiation. This study explored how CD38+ NK cells regulated CD4+ T-cell differentiation into Treg cells in RA.MethodsProportions of CD38+ NK cells and their counterpart CD38+ NK-like T (CD3+ CD16+ CD38+ CD56+) cells were measured in RA and rats with collagen-induced arthritis (CIA). CD38+ NK cells and CD38+ NK-like T cells were cocultured with CD4+ T cells, respectively.ResultsA significantly increased proportion of CD38+ NK cells and a decreased proportion of CD38+ NK-like T cells were detected in RA and CIA blood and synovial fluids. When CD4+ T cells were cocultured with CD38+ NK cells, mammalian target of rapamycin (mTOR) signaling was activated, and Th1/Th2 and Th17/Treg ratios were increased. When CD38+ NK cells were pretreated with anti-CD38 antibody, Treg cell proportion was increased, and Th1/Th2 and Th17/Treg ratios were decreased. CD38+ NK-like T cells showed the opposite results. CD38+ NK cells and CD38+ NK-like-T cells activated differential gene expressions and pathways in CD4+ T cells and initiated Th1 and Th2 cell differentiation by differential gene nodes.ConclusionsThis study suggest that the high CD38+ NK cell proportion and low CD38+ NK-like T cell proportion in RA suppress Treg cell differentiation by stimulating mTOR signaling in CD4+ T cells, which consequentially disturbs the immune tolerance. |
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Keywords: | Cluster of differentiation 38 Collagen-induced arthritis CD38+ NK cells CD38+ NK-like T cells Immune tolerance Rheumatoid arthritis Treg cells |
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