15d-PGJ2 ameliorates collagen-induced arthritis by convergence of Th17 to induced-Tregs (83.1)

Abstract

Abstract Regulatory T cells (Treg) are CD4+T subtype cells with a critical role in inhibiting autoimmunity. Several works reported efficacy therapeutic of 15d-PGJ2 in autoimmune models as well in vitro is able to generate the differentiation of naïve T lymphocytes to the regulatory profile. However, this prostanoid use and its interrelationship with Tregs during the arthritis rheumatoid are unknown. In view of a therapeutic perspective, we investigate the potential role of 15d-PGJ2 in a model of collagen-induced arthritis (CIA) and its interplay with Tregs-induced anti-inflammatory mechanism. CIA was elicited in DBA male mice by collagen-emulsion injection and then treated with 15-PGJ2 daily during 7 days. 15d-PGJ2 administration at the disease onset attenuated the severity of CIA, reducing clinical score, pain and edema. Furthermore, while the mRNA expression of ROR-γt was reduced, FOXP3 expression was up-regulated in draining lymph nodes cells from 15d-PGJ2-treated mice. In vitro, 15-PGJ2 increased the expression of FOXP3, GITR and CTLA-4, Tregs makers, on CD4+CD25- population, suggesting the induction of Tregs on effector cells. Coculture of Th17 cells with 15d-PGJ2-induced Treg reduced significantly the IL-17 production by collagen and α-CD3 stimuli whereas IL-10 production was enhanced. 15d-PGJ2 converge Th17 lymphocytes to regulatory profile, reducing the number of pathogenic T cells and consequently suppressing the inflammatory immune response. FAPEMIG 097/09