COMPOSITIONS AND METHODS FOR MODULATING CGRP SIGNALING TO REGULATE INNATE LYMPHOID CELL INFLAMMATORY RESPONSES

摘要

The present invention provides novel compositions and methods based on the discovery of the mechanisms and gene expression programs associated with homeostatic ILC2s and proinflammatory ILC2s that drive tissue inflammation. Molecular cues were identified that modulate ILC responses to alarmins using single-cell RNA-sequencing (scRNA-seq) profiles of lung-resident ILCs at steady state and after in vivostimulation. The neuropeptide CGRP and the CGRP receptor were identified as expressed on ILC2s. Treatment with CGRP reduces allergic lung inflammation and reduces the proliferation and expansion of ILC2 cells. The results demonstrate that CGRP signaling strongly modulates ILC2 responses and highlights the importance of neuro-immune crosstalk in allergic inflammatory responses at mucosal surfaces.