*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 T_H1 and T_H17 CD4⁺ T cells in systemic erythematosus lupus (SLE)-like chronic graft-versus-host disease

*Methods: Female C57BL/6 (H-2^b) mice were purchased from Orient. CD137^-/- (H-2^b) and B6.C-H2^bm12 (H-2^bm12) 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 (T_FH) 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.

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