Galectin-9-CD44 Interaction Enhances Stability and Function of Adaptive Regulatory T Cells

Author(s)

Wu, Chuan ^[1] ; Thalhamer, Theresa ^[1] ; Franca, Rafael F. ^[1] ; Xiao, Sheng ^[1] ; Wang, Chao ^[1] ; Hotta, Chie ^[1] ; Zhu, Chen ^[1] ; Hirashima, Mitsuomi ^[2] ; Anderson, Ana C. ^[1] ; Kuchroo, Vijay K. ^[1]

Affiliation

^[1] Harvard Univ, Brigham & Womens Hosp, Sch Med, Evergrande Ctr Immunol Dis, Boston, MA 02115 - USA

^[2] Kagawa Univ, Fac Med, Dept Immunol & Immunopathol, Kagawa 7610793 - Japan

• Document type: Journal article
• Source: IMMUNITY; v. 41, n. 2, p. 270-282, AUG 21 2014.
• Web of Science Citations: 85

Abstract

The beta-galactoside-binding protein galectin-9 is critical in regulating the immune response, but the mechanism by which it functions remains unclear. We have demonstrated that galectin-9 is highly expressed by induced regulatory T cells (iTreg) and was crucial for the generation and function of iTreg cells, but not natural regulatory T (nTreg) cells. Galectin-9 expression within iTreg cells was driven by the transcription factor Smad3, forming a feed-forward loop, which further promoted Foxp3 expression. Galectin-9 increased iTreg cell stability and function by directly binding to its receptor CD44, which formed a complex with transforming growth factor-beta (TGF-beta) receptor I (TGF-beta RI), and activated Smad3. Galectin-9 signaling was further found to regulate iTreg cell induction by dominantly acting through the CNS1 region of the Foxp3 locus. Our data suggest that exogenous galectin-9, in addition to being an effector molecule for Treg cells, acts synergistically with TGF-beta to enforce iTreg cell differentiation and maintenance. (AU)

• FAPESP's process: 12/14924-7 - Role of NOD2 signaling and molecular mechanisms involved in the generation of IL-17 pathogenic T cells in autoimmune diseases
• Grantee: Rafael Freitas de Oliveira Franca
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor