CGRP restrains CD4⁺ T cell responses and allergic sensitization

Area of Science:

• Neuroimmunology
• Allergy and Immunology

Background:

• Calcitonin gene-related peptide (CGRP) is a neuropeptide involved in immune regulation, but its role in adaptive immunity is not well understood.
• The CGRP-RAMP1 pathway is identified as a critical intrinsic regulator of CD4+ T cell responses during allergic sensitization.

Purpose of the Study:

• To investigate the role of the CGRP-RAMP1 pathway in regulating CD4+ T cell responses during allergic sensitization.
• To determine the therapeutic potential of CGRP in mitigating allergic asthma.

Main Methods:

• Induction of allergic sensitization using house dust mite (HDM) in mice.
• Analysis of CGRP+ sensory nerve fiber distribution and RAMP1 expression on immune cells.
• Utilizing techniques like TCR-seq, parabiosis, adoptive transfer, flow cytometry, ATAC-seq, and RNA-seq to study CD4+ T cell function.
• Employing CD4+ T cell-specific RAMP1 knockout mice and CGRP treatment in HDM-induced allergic asthma models.

Main Results:

• CGRP-RAMP1 signaling suppresses CD4+ T cell activation and differentiation, and represses Tfh-associated gene expression.
• Reduced CGRP+ fiber density in lymph nodes during allergic sensitization.
• CD4+ T cell-specific RAMP1 deficiency exacerbates allergic sensitization by promoting Tfh cell accumulation.
• Exogenous CGRP treatment mitigates allergic sensitization and alleviates allergic asthma in a RAMP1-dependent manner.

Conclusions:

• The CGRP-RAMP1 pathway acts as a neuroimmune axis, restraining allergic sensitization by directly modulating CD4+ T cell immunobiology.
• CGRP treatment demonstrates therapeutic potential for allergic asthma by targeting this neuroimmune pathway.