Differential role of all-trans retinoic acid in promoting the development of CD4+ and CD8+ regulatory T cells. Issue 2 (30th September 2013)

• Record Type: Journal Article
• Authors: Ma, Jilin; Liu, Ya; Li, Yang; Gu, Jian; Liu, Justin; Tang, Jiayou; Wang, Julie; Ryffel, Bernhard; Shen, Yi; Brand, David; Liu, Zhongmin; Zheng, Song Guo
• Is Part Of: Journal of leukocyte biology. Volume 95:Issue 2(2014)
• Page Start: 275
• Page End: 283
• Publication Date: 2013-09-30
• Subjects: TGF-β -- all-trans retinoic acid -- regulatory T cells -- Foxp3 -- Autoimmunity -- GVHD; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.0513297
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : The differential role of at RA in promoting CD4 + - and CD8 + -induced Tregs; a caution for a protocol in developing Treg therapy in clinic. ABSTRACT: It is known that ATRA promotes the development of TGF-β-induced CD4 + Foxp3 + iTregs, which play a vital role in the prevention of autoimmune diseases; however, the role of ATRA in facilitating the differentiation and function of CD8 + Foxp3 + iTregs remains elusive. Using a head-to-head comparison, we found that ATRA promoted expression of Foxp3 and development of CD4 + iTregs, but it did not promote Foxp3 expression on CD8 + cells. Using a standard in vitro assay, we demonstrated that CD8 + iTregs induced by TGF-β and ATRA were not superior to CD8 + iTregs induced by TGF-β alone. In cGVHD, in a typical lupus syndrome model where DBA2 spleen cells were transferred to DBA2xC57BL/6 F1 mice, we observed that both CD8 + iTregs induced by TGF-β and ATRA and those induced by TGF-β alone had similar therapeutic effects. ATRA did not boost but, conversely, impaired the differentiation and function of human CD8 + iTregs. CD8 + cells expressed the ATRA receptor RAR and responded to ATRA, similar to CD4 + cells. We have identified the differential role of ATRA in promoting Foxp3 + Tregs in CD4 + and CD8 + cell populations. These results will help to determine a protocol for developing different Treg cell populations and may provide novel insights into clinical cell therapy for patients with autoimmune diseases and those needing organ transplantation.