Differential role of all-trans retinoic acid in promoting the development of CD4+ and CD8+ regulatory T cells

Jilin Ma, Ya Liu, Yang Li, Jian Gu, Justin Liu, Jiayou Tang, Julie Wang, Bernhard Ryffel, Yi Shen, David Brand, Zhongmin Liu, Song Guo Zheng

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)275-283
Number of pages9
JournalJournal of Leukocyte Biology
Issue number2
StatePublished - Feb 2014

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Cell Biology


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