A role for BATF3 in T_H9 differentiation and T-cell-driven mucosal pathologies

Area of Science:

• Immunology
• Molecular Biology

Background:

• T helper 9 (T_H9) cells are implicated in inflammatory and allergic diseases.
• The precise molecular mechanisms regulating T_H9 cell differentiation remain incompletely understood.

Purpose of the Study:

• To identify novel inducers of T_H9 cell differentiation.
• To elucidate the role of TL1A and associated transcription factors in T_H9 cell function and inflammatory responses.

Main Methods:

• Investigated the effect of TL1A on mouse and human T_H9 cell differentiation in vitro.
• Analyzed the expression and function of transcription factors BATF and BATF3.
• Utilized a T-cell transfer model to assess in vivo inflammatory responses.
• Employed neutralizing IL-9 antibodies and Batf3-deficient T cells.

Main Results:

• TL1A was identified as a potent inducer of T_H9 cell differentiation, enhancing IL-9 secretion.
• TL1A upregulated BATF and BATF3, which are crucial for IL-9 promoter binding and IL-9 production.
• BATF and BATF3 deficiency impaired IL-9 secretion.
• In vivo, TL1A promoted IL-9-dependent intestinal and lung inflammation mediated by T_H9 cells.
• Neutralization of IL-9 or deficiency in BATF3 attenuated TL1A-driven mucosal inflammation.

Conclusions:

• TL1A is a critical regulator of T_H9 cell differentiation and function.
• BATF3 plays a significant role in TL1A-induced T_H9 cell-mediated mucosal inflammation.
• Targeting the TL1A-BATF3 axis may offer therapeutic strategies for inflammatory diseases.