Cutting edge: all-trans retinoic acid sustains the stability and function of natural regulatory T cells in an inflammatory milieu

• Published in: The Journal of immunology (1950) 2010-09, Vol.185 (5), p.2675-2679
• Main Authors: Zhou, Xiaohui, Kong, Ning, Wang, Julie, Fan, Huiming, Zou, Hejian, Horwitz, David, Brand, David, Liu, Zhongmin, Zheng, Song Guo
• Format: Article
• Language: English
• Subjects: Animals; Arthritis, Experimental - immunology; Arthritis, Experimental - metabolism; Arthritis, Experimental - pathology; Autoimmune Diseases - immunology; Autoimmune Diseases - metabolism; Autoimmune Diseases - pathology; Cells, Cultured; Female; Forkhead Transcription Factors - biosynthesis; Gene Knock-In Techniques; Immunity, Innate - genetics; Immunophenotyping; Inflammation Mediators - pharmacology; Inflammation Mediators - physiology; Interleukin-17 - biosynthesis; Interleukin-6 - pharmacology; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; T-Lymphocytes, Helper-Inducer - immunology; T-Lymphocytes, Helper-Inducer - metabolism; T-Lymphocytes, Helper-Inducer - pathology; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; T-Lymphocytes, Regulatory - pathology; Tretinoin - pharmacology; Tretinoin - physiology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1000598

Recent studies have demonstrated that plasticity of naturally occurring CD4(+)Foxp3(+) regulatory T cells (nTregs) may account for their inability to control chronic inflammation in established autoimmune diseases. All-trans retinoic acid (atRA), the active derivative of vitamin A, has been demonstrated to promote Foxp3(+) Treg differentiation and suppress Th17 development. In this study, we report a vital role of atRA in sustaining the stability and functionality of nTregs in the presence of IL-6. We found that nTregs treated with atRA were resistant to Th17 and other Th cell conversion and maintained Foxp3 expression and suppressive activity in the presence of IL-6 in vitro. atRA decreased IL-6R expression and signaling by nTregs. Of interest, adoptive transfer of nTregs even from arthritic mice treated with atRA suppressed progression of established collagen-induced arthritis. We suggest that nTregs treated with atRA may represent a novel treatment strategy to control established chronic immune-mediated inflammatory diseases.