Menin Controls the Memory Th2 Cell Function by Maintaining the Epigenetic Integrity of Th2 Cells

Area of Science:

• Immunology
• Epigenetics
• Molecular Biology

Background:

• Posttranslational histone modifications are crucial epigenetic regulators of gene expression.
• The Trithorax group (TrxG) complex mediates gene transcription induction and maintenance.
• Menin is a component of the TrxG complex with a known role in epigenetic regulation.

Purpose of the Study:

• To investigate the role of Menin in the acquisition and maintenance of T helper 2 (Th2) cell identity.
• To elucidate Menin's function in Th2-specific gene regulation and its impact on immune responses.

Main Methods:

• Utilized T cell-specific Menin-deficient mice for in vivo studies.
• Performed gene expression analysis to assess Menin's impact on Th2-related genes.
• Investigated Menin's direct binding to the Gata3 gene locus.

Main Results:

• Menin primarily maintains high expression of established Th2-specific genes, rather than inducing them.
• A Menin-Gata3 axis was identified as a core component of the Th2 gene regulatory network.
• Menin deficiency attenuated Th2 cell-induced airway inflammation in both effector and memory T cells.

Conclusions:

• Menin plays a critical role in maintaining Th2 cell identity and function.
• The Menin-Gata3 axis is essential for the Th2-specific gene regulatory network.
• Menin is vital for Th2 cell-mediated immune responses, particularly in controlling airway inflammation.