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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

Full text
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]
Total Authors: 10
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
Total Affiliations: 2
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