The neuroimmune CGRP-RAMP1 axis tunes cutaneous adaptive immunity to the microbiota

• 成果类型: Article
• 署名作者: Kulalert, Warakorn; Wells, Alexandria C.; Link, Verena M.; Lim, Ai Ing; Bouladoux, Nicolas; Nagai, Motoyoshi; Harrison, Oliver J.; Kamenyeva, Olena; Kabat, Juraj; Enamorado, Michel; Chiu, Isaac M.; Belkaid, Yasmine
• 署名单位: National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); National Institutes of Health (NIH) - USA; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); Icahn School of Medicine at Mount Sinai; Icahn School of Medicine at Mount Sinai; Harvard University; Harvard Medical School; Pasteur Network; Universite Paris Cite; Institut Pasteur Paris
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9828
• DOI: 10.1073/pnas.2322574121
• 发表日期: 2024-03-07
• 关键词: gene-related peptide; innate lymphoid-cells; sensory neurons; negative regulation; skin immunity; physiology; responses; receptor; transcription; homeostasis

摘要

The somatosensory nervous system surveils external stimuli at barrier tissues, regulating innate immune cells under infection and inflammation. The roles of sensory neurons in controlling the adaptive immune system, and more specifically immunity to the microbiota, however, remain elusive. Here, we identified a mechanism for direct neuroimmune communication between commensal- specific T lymphocytes and somatosensory neurons mediated by the neuropeptide calcitonin gene-related peptide (CGRP) in the skin. Intravital imaging revealed that commensal- specific T cells are in close proximity to cutaneous nerve fibers in vivo. Correspondingly, we observed upregulation of the receptor for the neuropeptide CGRP, RAMP1, in CD8+ T lymphocytes induced by skin commensal colonization. The neuroimmune CGRP-RAMP1 signaling axis functions in commensal- specific T cells to constrain Type 17 responses and moderate the activation status of microbiota- reactive lymphocytes at homeostasis. As such, modulation of neuroimmune CGRP-RAMP1 signaling in commensal-specific T cells shapes the overall activation status of the skin epithelium, thereby impacting the outcome of responses to insults such as wounding. The ability of somatosensory neurons to control adaptive immunity to the microbiota via the CGRP-RAMP1 axis underscores the various layers of regulation and multisystem coordination required for optimal microbiota- reactive T cell functions under steady state and pathology.