Format

Send to

Choose Destination
Immunity. 2014 Aug 21;41(2):270-82. doi: 10.1016/j.immuni.2014.06.011. Epub 2014 Jul 24.

Galectin-9-CD44 interaction enhances stability and function of adaptive regulatory T cells.

Author information

1
Evergrande Center for Immunologic Diseases, Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115, USA.
2
Department of Immunology and Immunopathology, Faculty of Medicine, Kagawa University, Kagawa 761-0793, Japan.
3
Evergrande Center for Immunologic Diseases, Harvard Medical School, Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address: vkuchroo@rics.bwh.harvard.edu.

Abstract

The β-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-β (TGF-β) receptor I (TGF-βRI), 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-β to enforce iTreg cell differentiation and maintenance.

PMID:
25065622
PMCID:
PMC4219323
DOI:
10.1016/j.immuni.2014.06.011
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms

Substances

Grant support

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center