Research Article Therapeutic Treatment of Arthritic Mice with 15-Deoxy Δ 12,14 -Prostaglandin J 2 (15d-PGJ 2 ) Ameliorates Disease through the Suppression of Th17 Cells and the Induction of CD4 + CD25 - FOXP3 + Cells Vanessa Carregaro, 1 Marcelo H. Napimoga, 2 Raphael S. Peres, 1 Luciana Benevides, 1 Laís Amorim Sacramento, 1 Larissa G. Pinto, 3 Renata Grespan, 3 Thiago M. Cunha, 3 João Santana da Silva, 1 and Fernando Q. Cunha 1,3 1 Department of Biochemistry and Immunology, School of Medicine of Ribeir˜ ao Preto, 14049-900 Ribeir˜ ao Preto, SP, Brazil 2 Laboratory of Immunology and Molecular Biology, S˜ ao Leopoldo Mandic Institute and Research Center, 13045755 Campinas, SP, Brazil 3 Department of Pharmacology, School of Medicine of Ribeir˜ ao Preto, 14049-900 Ribeir˜ ao Preto, SP, Brazil Correspondence should be addressed to Fernando Q. Cunha; fdqcunha@fmrp.usp.br Received 9 March 2016; Revised 20 July 2016; Accepted 4 August 2016 Academic Editor: Constantino L´ opez-Mac´ ıas Copyright © 2016 Vanessa Carregaro et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Te prostaglandin, 15-deoxy Δ 12,14 -prostaglandin J 2 (15d-PGJ 2 ), is a lipid mediator that plays an important role in the control of chronic infammatory disease. However, the role of prostanoid in rheumatoid arthritis (RA) is not well determined. We demonstrated the therapeutic efect of 15d-PGJ 2 in an experimental model of arthritis. Daily administration of 15d-PGJ 2 attenuated the severity of CIA, reducing the clinical score, pain, and edema. 15d-PGJ 2 treatment was associated with a marked reduction in joint levels of proinfammatory cytokines. Although the mRNA expression of ROR-t was profoundly reduced, FOXP3 was enhanced in draining lymph node cells from 15d-PGJ 2 -treated arthritic mice. Te specifc and polyclonal CD4 + T17 cell responses were limited during the addition of prostaglandin to cell culture. Moreover, in vitro 15d-PGJ 2 increased the expression of FOXP3, GITR, and CTLA-4 in the CD4 + CD25 − population, suggesting the induction of Tregs on conventional T cells. Prostanoid addition to CD4 + CD25 − cells selectively suppressed T17 diferentiation and promoted the enhancement of FOXP3 under polarization conditions. Tus, 15d-PGJ 2 ameliorated symptoms of collagen-induced arthritis by regulating T17 diferentiation, concomitant with the induction of Tregs, and, consequently, protected mice from diseases aggravation. Altogether, these results indicate that 15d-PGJ 2 may represent a potential therapeutic strategy in RA. 1. Introduction Rheumatoid arthritis (RA) is a chronic disorder characterized by chronic systemic infammation and progressive destruc- tion of cartilage and bone. Te etiology of RA is unknown, but proinfammatory cytokines play a central role in the disease development and perpetuation [1]. Among several cytokines, IL-17 is expressed in the synovial tissue of RA patients and animals models and had been implicated in the initiation and progression of arthritis [2]. In murine arthritis models, IL-17 promotes the activation of synovial fbroblasts and both leukocyte emigration and activation, resulting in the production of several infammatory mediators and tissue lesions. For example, IL-17 has been shown to enhance joint infammation and the tissue production of cytokines (TNF- , IL-1) [3], chemokines (MIP-2/CXCL2, KC/CXCL1, and IL-8/CXCL8), and matrix metalloproteinases [4]. Given the ability of IL-17 to promote RA pathology, it is plausible to suggest that pharmacologic strategies aimed at blocking or suppressing IL-17, particularly cellular T17 function, may Hindawi Publishing Corporation Mediators of Inflammation Volume 2016, Article ID 9626427, 13 pages http://dx.doi.org/10.1155/2016/9626427