Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: Although CD137 is well known as a costimulatory receptor in T cells, limited information is available for its immunoregulatory function. Here, we report that CD137 signaling maintains CD11b+ regulatory dendritic cells (DCs) that can suppress activation of donor TH1 and TH17 CD4+ T cells in systemic erythematosus lupus (SLE)-like chronic graft-versus-host disease
*Methods: Female C57BL/6 (H-2b) mice were purchased from Orient. CD137-/- (H-2b) and B6.C-H2bm12 (H-2bm12) mice were bred at the animal facility of the Biomedical Research Center at University of Ulsan. All of mice were used at 8-10 wks of age. Single-cell suspensions in PBS were prepared from the spleens and lymph nodes of female bm12 mice. The erythrocytes were lysed in RBC lysis buffer (BioLegend), the remaining cells were re-suspended at 8 x 107 cells/0.2 ml in PBS. Chronic GVHD was induced by transfer of 8 x 107 of bm12 cells into the tail vein of female wild-type and CD137-/- mice. Immediately thereafter, 200 μg of anti-CD137 mAb (3E1) or control Ig was intraperitoneally administered. And then we check the flowcytometry, ELISA, RT PCR, and liver and colonic histology.
*Results: Deletion of CD137 in recipient mice shifted the disease phenotype toward acute GVHD, which was caused by activation of donor T cells and subsequent multiple organ. CD137-/- recipients had had characteristic changes associated with acute GVHD: 1) there were defects in differentiation of T follicular helper (TFH) cells, germinal-center B cells, and plasma cells, and in production of anti-DNA IgG1 autoantibody; 2) their splenic DCs showed dysregulated expression of DC-specific transcription factors and proinflammatory genes; and 3) there were strong activation of donor T cells but decreased Treg cells in the CD137-/- recipient spleen. CD11b+ splenic DCs stimulated with anti-CD137 antibody and CpG markedly increased expression of immunomodulatory genes and such regulatory DCs inhibited acute GVHD in CD137-/- recipients. Their suppressive action was mediated through IL-10 that is indispensable for the induction and expansion of peripheral of Treg cells.
*Conclusions: . In conclusion, our study identifies CD137 signaling in DCs as an important braking point to prevent systemic inflammation and this control system may be considered as a therapeutic strategy for a variety of inflammatory and autoimmune diseases.
To cite this abstract in AMA style:Cho H, Lee J, Kwon B, Park S, Park H, Yoo K, Park K, Kim J. CD137 Signaling in Regulatory Dendritic Cells Is Required for Suppressing a Systemic Inflammation in the bm12-Inducible Model of Systemic Lupus Erythematosus [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/cd137-signaling-in-regulatory-dendritic-cells-is-required-for-suppressing-a-systemic-inflammation-in-the-bm12-inducible-model-of-systemic-lupus-erythematosus/. Accessed September 22, 2021.
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