Three’s company: The cooperative signals behind the differentiation of Th9 cells. J Alejandra Rodriguez

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Semin Immunol. 2025 Oct 16;80:101999. doi: 10.1016/j.smim.2025.101999. Online ahead of print.

ABSTRACT

T helper 9 (Th9) cells, characterized by their production of interleukin-9 (IL-9), play pivotal roles in protective immunity and inflammatory disease. Their differentiation depends on the integration of three signals: TCR engagement (Signal 1), co-stimulatory receptor activation (Signal 2), and cytokine-driven transcriptional programming (Signal 3). This review explores how these signals converge to shape Th9 identity, highlighting the unique requirement for strong TCR signaling, heightened sensitivity to NF-κB signaling pathways, and the interplay of cytokine/STAT proteins. Understanding these mechanisms offers insights into Th9 biology and therapeutic strategies for cancer, allergy, and autoimmune disease.

PMID:41106133 | DOI:10.1016/j.smim.2025.101999

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