Effect of calcitonin gene-related peptide on group 2 innate lymphoid cell in allergic rhinitis

Allergic rhinitis (AR) affects ~ 40% of the global population and is linked to IgE-mediated immunologic response. Group 2 innate lymphoid cells (ILC2s) exert a pivotal function in AR pathogenesis. Calcitonin gene-related peptide (CGRP) serves as a conduit between neural and immune regulatory pathways. Our objective was to explore the impact of calcitonin gene-related peptide (CGRP) on the proliferative capacity and functional characteristics of ILC2s in the context of AR. Fifteen AR patients were recruited. Nasal lavage fluid (NLF) and peripheral blood mononuclear cells (PBMCs) were collected. ILC2s were sorted and stimulated with CGRP, IL-33, and VX745. The proliferation and function of ILC2s were determined. A significant elevation in CGRP protein levels was observed in NLF of AR patients compared to healthy controls. CGRP positively correlated with IL-5, IL-13 expression, and total nasal symptom score (TNSS). CGRP upregulated Calcrl and Ramp1 mRNA expression in ILC2s and stimulated their proliferation and GATA-3, RORα expression. However, CGRP alone did not affect type 2 cytokine secretion by ILC2s. Targeting CGRP to inhibit proliferation of ILC2s may be a viable therapeutic strategy for treating AR.