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Sci Immunol. 2018 Oct 5;3(28). pii: eaat9453. doi: 10.1126/sciimmunol.aat9453.

The cysteinyl leukotriene 3 receptor regulates expansion of IL-25-producing airway brush cells leading to type 2 inflammation.

Author information

1
Division of Rheumatology, Immunology and Allergy, Jeff and Penny Vinik Center for Allergic Disease Research, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. lbankova@bwh.harvard.edu nbarrett@bwh.harvard.edu.
2
Division of Rheumatology, Immunology and Allergy, Jeff and Penny Vinik Center for Allergic Disease Research, Brigham and Women's Hospital and Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
3
Department of Immunology, University of Washington School of Medicine, Seattle, WA 98109, USA.

Abstract

Respiratory epithelial cells (EpCs) orchestrate airway mucosal inflammation in response to diverse environmental stimuli, but how distinct EpC programs are regulated remains poorly understood. Here, we report that inhalation of aeroallergens leads to expansion of airway brush cells (BrCs), specialized chemosensory EpCs and the dominant epithelial source of interleukin-25 (IL-25). BrC expansion was attenuated in mice lacking either LTC4 synthase, the biosynthetic enzyme required for cysteinyl leukotriene (CysLT) generation, or the EpC receptor for leukotriene E4 (LTE4), CysLT3R. LTE4 inhalation was sufficient to elicit CysLT3R-dependent BrC expansion in the murine airway through an IL-25-dependent but STAT6-independent signaling pathway. Last, blockade of IL-25 attenuated both aeroallergen and LTE4-elicited CysLT3R-dependent type 2 lung inflammation. These results demonstrate that CysLT3R senses the endogenously generated lipid ligand LTE4 and regulates airway BrC number and function.

PMID:
30291131
DOI:
10.1126/sciimmunol.aat9453

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