Activation of CD81+ skin ILC2s by cold-sensing TRPM8+ neuron-derived signals maintains cutaneous thermal homeostasis

Ming Xu, Chao Li, Jie Yang, Amy Ye, Liping Yan, Beng San Yeoh, Lai Shi, Yu Shin Kim, Joonsoo Kang, Matam Vijay-Kumar, Na Xiong

Research output: Contribution to journalArticlepeer-review

Abstract

As the outermost barrier tissue of the body, the skin harbors a large number of innate lymphoid cells (ILCs) that help maintain local homeostasis in the face of changing environments. How skin-resident ILCs are regulated and function in local homeostatic maintenance is poorly understood. We here report the discovery of a cold-sensing neuron-initiated pathway that activates skin group 2 ILCs (ILC2s) to help maintain thermal homeostasis. In stearoyl-CoA desaturase 1 (SCD1) knockout mice whose skin is defective in heat maintenance, chronic cold stress induced excessive activation of CCR10CD81+ST2+ skin ILC2s and associated inflammation. Mechanistically, stimulation of the cold-sensing receptor TRPM8 expressed in sensory neurons of the skin led to increased production of IL-18, which, in turn, activated skin ILC2s to promote thermogenesis. Our findings reveal a neuroimmune link that regulates activation of skin ILC2s to support thermal homeostasis and promotes skin inflammation after hyperactivation.

Original languageEnglish (US)
Article numbereabe0584
JournalScience Immunology
Volume7
Issue number72
DOIs
StatePublished - May 2022

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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