Synthetic TGF-β Signaling Agonist-Treated Dendritic Cells Induce Tolerogenicity and Antirheumatic Effects

• Published in: Current issues in molecular biology 2022-08, Vol.44 (9), p.3809-3821
• Main Authors: Oh, Ji-Soo, Hwang, Sung-Uk, Noh, Kyung-Eun, Lee, Jun-Ho, Choi, So-Yeon, Nam, Ji-Hee, Song, Min-Seon, Jung, Nam-Chul, Song, Jie-Young, Seo, Han Geuk, Lim, Dae-Seog
• Format: Article
• Language: English
• Subjects: autoimmune diseases; dendritic cells; regulatory T cells; rheumatoid arthritis; TGF-β signaling
• ISSN: 1467-3045; 1467-3037; 1467-3045
• DOI: 10.3390/cimb44090261

The newly synthesized compound TGF-β signaling agonist (T74) is a small molecule associated with the TGF-β receptor signaling pathway. Tolerogenic dendritic cells (tDCs) have been used to examine immunosuppressive and anti-inflammatory effects in multiple autoimmune disease models. The aim of this study was to investigate whether treatment of DCs with T74 has an antirheumatic effect in a mouse model of collagen-induced arthritis (CIA). Bone marrow-derived cells were obtained from DBA/1J mice and differentiated into DCs. T74-treated DCs (T74-DCs) were generated by treating bone marrow-derived DCs with LPS, type II collagen, and T74. T74-DCs expressed lower levels of surface molecules and inflammatory cytokines associated with antigen presentation and T cell stimulation. The ability of T74-DCs to differentiate effector T cells was lower than that of T74-untreated DCs (NT-DCs), but T74-DCs increased the regulatory T (Treg) cell differentiation in vitro. DBA/1J mice received two subcutaneous (s.c.) injections of type II collagen to establish CIA. Mice then received two s.c. injections of T74-DCs or NT-DCs. Joint inflammation was ameliorated in the paws of T74-DC-treated mice. Additionally, Treg populations in T74-DC-treated mice were higher than in NT-DC-treated or PBS-treated CIA mice. Taken together, these results demonstrate that T74 induces tolerance in DCs, and that T74-mediated DCs exert antirheumatic effects via induction of Tregs.