CD4+CD126low/− Foxp3+ Cell Population Represents a Superior Subset of Regulatory T Cells in Treating Autoimmune Diseases

Ye Chen, Zhenjian Xu, Rongzhen Liang, Julie Wang, Anping Xu, Ning Na, Bin Li, Ruoning Wang, Miller Joseph, Nancy Olsen, Willa Hsueh, Song Guo Zheng

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


CD4+Foxp3+ regulatory T (Treg) cells are crucial for maintaining homeostasis and preventing autoimmune diseases. Nonetheless, we and others have previously reported that natural Treg cells are unstable and dysfunctional in the inflamed environment with a high-salt diet, limiting the Treg function in disease control. In this study, we made an innovative observation showing a high degree of heterogeneity within the Treg pool. We identified that CD126, interleukin (IL)-6 receptor alpha chain, contributed to Treg cell instability. Using a series of in vitro and in vivo experimental approaches, we demonstrated that CD126Lo/− Treg cells presented greater function and were more stable than CD126Hi nTreg cells, even in the presence of IL-6 and inflammation. Blockade of programmed death-1 (PD-1) interrupted CD126Lo/− nTreg cell stability. Additionally, CD126Lo/− Treg cells can treat colitis and established collagen-induced arthritis, while the CD126Hi cell population failed to do this. Moreover, we noted that CD126 expression of Treg cells had a positive correlation to rheumatoid arthritis (RA) severity and the stability of Treg cells. Our results strongly suggest that the manipulation of CD126Lo/− nTreg cells could be a novel strategy for the treatment of autoimmune diseases and for other conditions associated with a deficit of Treg cells.

Original languageEnglish (US)
Pages (from-to)2406-2416
Number of pages11
JournalMolecular Therapy
Issue number11
StatePublished - Nov 4 2020

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery


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