Systemic lupus erythematosus (SLE) is an autoimmune disease that involves multiple immune cell subsets. We analyzed immune cell subsets in human peripheral blood mononuclear cells (PBMC) in order to identify the cells that are significantly associated with SLE disease activity and treatment. The frequencies of various subsets of CD4 T cells, B cells, monocytes and NK cells in PBMC were assessed in 30 healthy controls (HC), 30 rheumatoid arthritis (RA) patients and 26 SLE patients using flow cytometry. The correlations between subset frequencies in SLE and clinical traits including Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) were examined. Changes in subset frequencies after the treatment in SLE patients were investigated. We focused on CD25LAG3 T cells and investigated their characteristics, including cytokine secretion, mRNA expression and suppression capacity. We assessed correlations between CD25LAG3 T cells and SLEDAI by Spearman's rank correlation coefficient. CD25LAG3 T cells were significantly increased in SLE whereas there were few in RA and HC groups. CD25LAG3 T cell frequencies were significantly correlated with SLEDAI and were increased in patients with a high SLEDAI score (> 10). CD25LAG3 T cells produced both IL-17 and FOXP3, expressed mRNA of both and and lacked suppressive capacity. CD25LAG3 T cells were associated with disease activity of SLE. CD25LAG3 T cells had features of both CD25FOXP3 regulatory T cells (CD25 Treg) and Th17. CD25LAG3 T cells could be associated with the inflammatory pathophysiology of SLE.
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http://dx.doi.org/10.3389/fimmu.2019.01619 | DOI Listing |
Sci Rep
May 2018
Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Programmed death ligand 1 (PD-L1)-mediated induction of immune tolerance has been vigorously investigated in autoimmunity and anti-tumor immunity. However, details of the mechanism by which PD-L1 is induced in CD4 T cells are unknown. Here, we revealed the potential function of Klf1 and Egr2-mediated induction of PD-L1 in CD4 T cells.
View Article and Find Full Text PDFFront Immunol
March 2019
Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Regulatory T cells (Tregs) are necessary for the maintenance of immune tolerance. Tregs are divided into two major populations: one is thymus derived and the other develops in the periphery. Among these Tregs, CD4CD25 Tregs, which mainly originate in the thymus, have been extensively studied.
View Article and Find Full Text PDFCurr Top Microbiol Immunol
June 2019
Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, Japan.
Regulatory T cells (Treg cells) play crucial roles in the induction of peripheral tolerance to self- and foreign-antigens. IL-10-producing regulatory T cells (IL-10-producing Treg cells) constitute a Treg cell subset characterized by the production of high amounts of IL-10, cytokine-mediated immunosuppressive capabilities, and independence of Foxp3 expression for their suppressive activity. In the past decade, identifying naturally occurring IL-10-producing Treg cells was difficult due to the lack of suitable surface markers.
View Article and Find Full Text PDFArthritis Res Ther
May 2017
Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
Background: Regulatory T cells (Tregs) play a role in the suppression of inflammation in autoimmune diseases, and lymphocyte activation gene 3 (LAG3) was reported as a marker of interleukin (IL)-10-producing Tregs. We aimed to clarify the function of human IL-10-producing CD4CD25LAG3 T cells (LAG3 Tregs) and their association with rheumatoid arthritis (RA).
Methods: LAG3 Tregs of human peripheral blood mononuclear cells (PBMCs) were cultured with B cells and follicular helper T cells to examine antibody suppression effects.
PLoS One
August 2017
Department of Allergy and Rheumatology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
TGF-β is a pleotropic cytokine involved in various biological processes. Of the three isoforms of TGF-β, TGF-β1 has long been recognized as an important inhibitory cytokine in the immune system and has been reported to inhibit B cell function in both mice and humans. Recently, it has been suggested that TGF-β3 may play an important role in the regulation of immune system in mice.
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