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Allergy

JAKs drive innate-like TH9 cell activation in allergy

Nature Reviews Immunology volume 23, page 344 (2023)Cite this article

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IL-9-producing T helper 9 (TH9) cells are associated with allergic diseases, including asthma, food allergy and atopic dermatitis. The mechanisms regulating these cells are incompletely understood — for instance, it is not clear why TH9 cells gradually lose the capacity to secrete IL-9. Here, Son et al. show that the IL9 locus becomes accessible to STAT5 and STAT6 shortly after TH9 cell differentiation and this enables TCR-independent ‘bystander’ activation of resting TH9 cells in response to IL-2 and IL-4. Such innate-like activation of TH9 cells promoted allergic airway inflammation in mice. Over time, chromatin remodelling reduces IL9 locus accessibility and limits IL9 expression, explaining the instability of TH9 cells. The authors suggest that intrinsic TH9 cell instability may act as a negative regulator of bystander activation, but this ‘checkpoint’ could break down in allergic disease. Notably, treatment with IL-2 and IL-4 induced IL-9 in circulating CD45RO+CD4+ T cells from patients with atopic dermatitis but not in corresponding T cells from healthy volunteers. Furthermore, expansion of TH9 cell populations was associated with STAT5 and STAT6 induction and responsiveness to JAK inhibitors both in mouse models and in patients with allergic disease. The authors suggest JAK inhibitors should be considered for patients whose allergic diseases are associated with expansion of TH9 cell populations.

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  1. Nature Reviews Immunology http://www.nature.com/nri/

    Yvonne Bordon

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  1. Yvonne Bordon
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Correspondence to Yvonne Bordon.

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Bordon, Y. JAKs drive innate-like TH9 cell activation in allergy. Nat Rev Immunol 23, 344 (2023). https://doi.org/10.1038/s41577-023-00887-5

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  • DOI: https://doi.org/10.1038/s41577-023-00887-5

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