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TH9 cells

JAKing up IL-9 expression in TH9 cells

Nature Immunology volume 24, pages 891–892 (2023)Cite this article

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Bystander activation that leads to expression of IL-9 in effector TH9 cells is induced by a TCR-independent, STAT-dependent mechanism and may represent a new strategy for therapeutic intervention to treat TH9-induced pathologies in vivo.

T helper 9 (TH9) cells perform a central protective role during parasitic infections and in anti-tumor immunity, but may contribute to the chronic inflammatory sequelae of autoimmune and allergic responses1. A distinctive feature of effector TH9 cells is phenotypic instability, characterized by transient expression of interleukin-9 (IL-9)2; however, upon re-activation by T cell antigen receptor (TCR) ligation, IL-9 can be effectively re-expressed in TH9 cells3. In this issue of Nature Immunology, Son et al.4 demonstrate a STAT5- and STAT6-dependent mechanism of IL9 induction in human and mouse resting TH9 cells. The authors identified epigenetic modifications that underlie the unstable phenotype observed in TH9 cells, and characterized a unique innate-like, TCR-independent IL9 induction in effector TH9 cells in vivo, pointing to JAK inhibitors (jakinibs) as an attractive strategy for therapeutic intervention in TH9-driven pathologies.

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Fig. 1: Bystander activation of resting TH9 cells by IL-2 and IL-4 promotes IL9 expression and TH9-driven inflammation in vivo.

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Acknowledgements

This work was supported by the Consejo Nacional de Ciencia y Tecnología (CONACYT) grant FORDECYT-PRONACE-303027 and DGAPA (IN220823-PAPIIT) to P.L.L. O.M.P received a fellowship from CONACYT (736162). We thank S. Erickson and I. Licona-Limón for critical reading of the manuscript.

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  1. Departamento de Biología Celular y del Desarrollo, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México City, México

    Ofelia Muñoz-Paleta & Paula Licona-Limón

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  1. Ofelia Muñoz-Paleta
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  2. Paula Licona-Limón
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Correspondence to Paula Licona-Limón.

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Muñoz-Paleta, O., Licona-Limón, P. JAKing up IL-9 expression in TH9 cells. Nat Immunol 24, 891–892 (2023). https://doi.org/10.1038/s41590-023-01509-x

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