Lymphocyte-activation gene 3+ (LAG3+) forkhead box protein 3- (FOXP3-) regulatory T cells induced by B cells alleviates joint inflammation in collagen-induced arthritis
Journal
Journal of Autoimmunity
Journal Volume
68
Pages
75-85
Date Issued
2016
Author(s)
Abstract
Rheumatoid arthritis (RA) is an autoimmune disease in which dysregulated immune cells primarily target synovial joints. Despite recent advances in the treatment of RA, including the introduction of biologic therapies and employment of combination disease-modifying antirheumatic drug strategies, remission rates remain suboptimal. Previous studies have demonstrated that the adoptive transfer of induced regulatory T cells (iTregs) was effective in treating a murine model of collagen-induced arthritis (CIA). The objective of this study was to develop optimal potential iTreg-based therapy for CIA by adoptively transferring LAG3+ Treg-of-B cells. B-cell-induced Treg-of-B cells expressed LAG3 but not Foxp3 (designated LAG3+ Treg-of-B), and secreted IL-4, IL-10, and TGF-β. Furthermore, LAG3+ Treg-of-B cells suppressed the proliferation of CD4+CD25- responder T cells through both LAG3 and IL-10 production. In the murine CIA model, adoptive transfer of LAG3+ Treg-of-B cells alleviated the joint severity as well as local and systemic inflammation. Treatment with LAG3+ Treg-of-B cells also promoted IL-10 production in lymphocytes isolated from the spleen and draining lymph nodes. Moreover, mice receiving LAG3+ Treg-of-B cell treatment showed significantly less pronounced osteolysis in the hind footpads, which correlated with the downregulation of tartrate-resistant acid phosphatase expression. In conclusion, we identified a novel subset of Tregs for CIA treatment. This insight may facilitate exploring novel regulatory T-cell-based therapies for human autoimmune diseases. ? 2016 Elsevier Ltd.
SDGs
Other Subjects
acid phosphatase tartrate resistant isoenzyme; CD4 antigen; interleukin 10; interleukin 2 receptor alpha; interleukin 4; transcription factor FOXP3; transforming growth factor beta; autacoid; CD223 antigen; cytokine; forkhead transcription factor; Foxp3 protein, mouse; leukocyte antigen; adoptive transfer; animal cell; animal experiment; animal model; animal tissue; Article; B lymphocyte; CD4+ CD25+ T lymphocyte; cell proliferation; cellular distribution; controlled study; disease severity; down regulation; foot pad; gene; gene expression; in vivo study; lymph node cell; lymphocyte activation gene 3; lymphocyte transfer; male; mouse; nonhuman; osteolysis; priority journal; real time polymerase chain reaction; regulatory T lymphocyte; rheumatoid arthritis; spleen cell; adoptive transfer; animal; Arthritis, Experimental; B lymphocyte; cell communication; genetics; immunology; immunomodulation; lymphocyte activation; metabolism; pathology; regulatory T lymphocyte; Adoptive Transfer; Animals; Antigens, CD; Arthritis, Experimental; B-Lymphocytes; Cell Communication; Cytokines; Forkhead Transcription Factors; Gene Expression; Immunomodulation; Inflammation Mediators; Lymphocyte Activation; Male; Mice; T-Lymphocytes, Regulatory
Publisher
Academic Press
Type
journal article