Distinct inflammatory Th17 subsets emerge in autoimmunity and infection

Area of Science:

• Immunology
• Cell Biology
• Pharmacology

Background:

• T helper 17 (Th17) cells are crucial in host defense and autoimmune diseases.
• Understanding the distinct roles of inflammatory Th17 cells remains a challenge.
• Mechanisms driving divergent functions of inflammatory Th17 cells are poorly understood.

Purpose of the Study:

• To distinguish inflammatory Th17 cell populations involved in autoimmune colitis versus infection.
• To investigate the differential response of these populations to clofazimine (CLF).
• To explore CLF's mechanism in selectively inhibiting pro-autoimmune Th17 cells.

Main Methods:

• Comparative analysis of Th17 cell populations from autoimmune colitis and infection models.
• Assessment of differential responses to clofazimine (CLF).
• Investigation of the role of ALDH1L2 in Th17 cell regulation by CLF.

Main Results:

• Inflammatory Th17 cells in autoimmune colitis and infection are distinguishable populations.
• Clofazimine (CLF) selectively inhibits pro-autoimmune Th17 cells.
• CLF preserves infection-elicited Th17 cell function partly by reducing ALDH1L2.
• Two distinct subsets within the inflammatory Th17 compartment exhibit unique regulatory mechanisms.

Conclusions:

• Inflammatory Th17 cells comprise distinct subsets with differing regulatory pathways.
• Clofazimine (CLF) demonstrates potential as a selective inhibitor for pro-autoimmune Th17 cells.
• Targeting disease-promoting Th17 cells offers a therapeutic strategy for autoimmune diseases.