A γδ T cell-IL-3 axis controls allergic responses through sensory neurons.

Autor: Flayer CH; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Kernin IJ; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Matatia PR; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.; Department of Immunology, Harvard Medical School, Boston, MA, USA., Zeng X; FM Kirby Center, Boston Children's Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA, USA., Yarmolinsky DA; FM Kirby Center, Boston Children's Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA, USA., Han C; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Naik PR; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Buttaci DR; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Aderhold PA; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Camire RB; Department of Immunology, Harvard Medical School, Boston, MA, USA., Zhu X; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Tirard AJ; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., McGuire JT; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Smith NP; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., McKimmie CS; Virus Host Interaction Team, Skin Research Centre, University of York, York, UK., McAlpine CS; Cardiovascular Research Institute and the Department of Medicine, Cardiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Friedman Brain Institute and the Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Swirski FK; Cardiovascular Research Institute and the Department of Medicine, Cardiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Woolf CJ; FM Kirby Center, Boston Children's Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA, USA., Villani AC; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA., Sokol CL; Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. clsokol@mgh.harvard.edu.
Jazyk: angličtina
Zdroj: Nature [Nature] 2024 Sep 04. Date of Electronic Publication: 2024 Sep 04.
DOI: 10.1038/s41586-024-07869-0
Abstrakt: In naive individuals, sensory neurons directly detect and respond to allergens, leading to both the sensation of itch and the activation of local innate immune cells, which initiate the allergic immune response 1,2 . In the setting of chronic allergic inflammation, immune factors prime sensory neurons, causing pathologic itch 3-7 . Although these bidirectional neuroimmune circuits drive responses to allergens, whether immune cells regulate the set-point for neuronal activation by allergens in the naive state is unknown. Here we describe a γδ T cell-IL-3 signalling axis that controls the allergen responsiveness of cutaneous sensory neurons. We define a poorly characterized epidermal γδ T cell subset 8 , termed GD3 cells, that produces its hallmark cytokine IL-3 to promote allergic itch and the initiation of the allergic immune response. Mechanistically, IL-3 acts on Il3ra-expressing sensory neurons in a JAK2-dependent manner to lower their threshold for allergen activation without independently eliciting itch. This γδ T cell-IL-3 signalling axis further acts by means of STAT5 to promote neuropeptide production and the initiation of allergic immunity. These results reveal an endogenous immune rheostat that sits upstream of and governs sensory neuronal responses to allergens on first exposure. This pathway may explain individual differences in allergic susceptibility and opens new therapeutic avenues for treating allergic diseases.
(© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Databáze: MEDLINE
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