title: Retinal attenuates inflammatory arthritis by reciprocal regulation of IL-17-producing T cells and Foxp3(+) regulatory T cells and the inhibition of osteoclastogenesis.
abstract: Retinoids (e.g., vitamin A and its derivatives) can regulate immune responses. The aim of this study was to determine whether all-trans retinaldehyde (retinal), a vitamin A derivative, can inhibit inflammatory responses and joint destruction in DBA/1J mice with collagen-induced arthritis (CIA). The arthritis score and incidence of arthritis were lower in mice treated with retinal compared to those treated with cottonseed oil. Histopathologic evidence of joint damage was lower in mice treated with retinal, corresponding with a reduction in the infiltration of immune cells in mice treated with retinal type II collagen (CII)-stimulated spleen cells. In addition, the expression of proinflammatory cytokines, oxidative stress proteins, and osteoclast markers were significantly reduced in mice treated with retinal. In vitro, retinal induced increased Foxp3 expression and inhibited Th17 development. The proportion of Foxp3(+) Treg cells was increased in the spleens of mice treated with retinal, whereas the proportion of Th17 cells was reduced. In both mice and a human culture system, tartrate-resistant acid phosphatase (TRAP) positive mononuclear cells and multinucleated cells were significantly reduced after treatment with retinal. The expression of osteoclast differentiation markers was dramatically decreased upon addition of retinal. This is the first study to demonstrate the therapeutic effect of retinal on an autoimmune arthritis model in mice through reciprocal regulation of Th17 and regulatory T cells and protection of differentiation and activation of osteoclasts. Taken together, our findings indicate that retinal has profound immunoregulatory functions and potential value for the treatment of autoimmune inflammatory disorders.
authors: The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, Seoul, South Korea.
authors: Mi-Kyung
authors: MK
authors: Park
authors: Joo-Yeon
authors: JY
authors: Jhun
authors: Seon-Yeong
authors: SY
authors: Lee
authors: Hye-Joa
authors: HJ
authors: Oh
authors: Min-Jung
authors: MJ
authors: Park
authors: Jae-Kyeong
authors: JK
authors: Byun
authors: Bo-Young
authors: BY
authors: Yoon
authors: Eun-Mi
authors: EM
authors: Park
authors: Dong-Gun
authors: DG
authors: Lee
authors: Seung-Ki
authors: SK
authors: Kwok
authors: Sung-Hwan
authors: SH
authors: Park
authors: Ho-Youn
authors: HY
authors: Kim
authors: Mi-La
authors: ML
authors: Cho
mesh_terms: D000135:Acid Phosphatase / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007527:Isoenzymes / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010010:Osteoclasts / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D012172:Retinaldehyde / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D000071681:Tartrate-Resistant Acid Phosphatase; D058504:Th17 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D020381:Interleukin-17; D007527:Isoenzymes; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D012172:Retinaldehyde