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

Autor: Ji-Soo Oh, Sung-Uk Hwang, Kyung-Eun Noh, Jun-Ho Lee, So-Yeon Choi, Ji-Hee Nam, Min-Seon Song, Nam-Chul Jung, Jie-Young Song, Han Geuk Seo, Younghwa Na, Dae-Seog Lim
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Current Issues in Molecular Biology, Vol 44, Iss 9, Pp 3809-3821 (2022)
Druh dokumentu: article
ISSN: 1467-3045
1467-3037
DOI: 10.3390/cimb44090261
Popis: 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.
Databáze: Directory of Open Access Journals
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