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

Area of Science:

• Immunology
• Molecular Biology

Background:

• Galectin-9 is a β-galactoside-binding protein involved in immune regulation.
• Its precise mechanism of action, particularly in T cell subsets, remains largely unknown.

Purpose of the Study:

• To elucidate the role and mechanism of galectin-9 in regulatory T cell differentiation and function.
• To investigate the molecular pathways influenced by galectin-9 in T cells.

Main Methods:

• Analysis of galectin-9 expression in induced regulatory T (iTreg) and natural regulatory T (nTreg) cells.
• Investigating the interaction of galectin-9 with CD44 and TGF-β receptor I (TGF-βRI).
• Assessing the impact of galectin-9 on Smad3 activation and Foxp3 expression.

Main Results:

• Galectin-9 is highly expressed in iTreg cells and is essential for their generation and function, but not nTreg cells.
• Galectin-9 expression is driven by Smad3, creating a feed-forward loop that enhances Foxp3 expression.
• Galectin-9 binds CD44, forming a complex with TGF-βRI to activate Smad3 and promote iTreg cell stability and function via the Foxp3 locus CNS1 region.

Conclusions:

• Galectin-9 plays a critical role in the differentiation and maintenance of iTreg cells.
• Exogenous galectin-9 synergizes with TGF-β to bolster iTreg cell induction and stability.