Interleukin-25 (IL-25) signals through the IL-17RA–IL-17RB receptor and has a key role in the pathogenesis of asthma. This study describes a unique population of type 2 cytokine-producing IL-17RB+CD11b+GR1mid myeloid cells (termed T2M cells) in mice with chronic allergic lung inflammation. Intratracheal administration of recombinant IL-25 induced the expression of the type 2 cytokines IL-4 and IL-13 specifically in T2M cells. Adoptive transfer of IL-25-treated T2M cells from wild-type mice to Il17rb−/− mice (which are IL-25 insensitive), together with the administration of recombinant IL-25, resulted in the induction of airway pathology. T2M cells were shown to be steroid resistant, as IL-25-induced pathology and type 2 cytokine expression were not reduced after treatment with dexamethasone. The authors identified a similar population of T2M cells in patients with asthma, suggesting that T2M cells may represent a new therapeutic target for this disease.
ORIGINAL RESEARCH PAPER
Petersen, B. C. et al. Interleukin-25 induces type 2 cytokine production in a steroid-resistant interleukin-17RB+ myeloid population that exacerbates asthmatic pathology. Nature Med. 18, 751–758 (2012)
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Afran, L. IL-25-responsive myeloid cells promote type 2 lung pathology. Nat Rev Immunol 12, 398 (2012). https://doi.org/10.1038/nri3239
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DOI: https://doi.org/10.1038/nri3239
