CGRP-related peptide adrenomedullin 2 from gut neurons promotes protective ILC2 responses and limits intestinal inflammation | Research

The takeaway

Enteric neurons produce adrenomedullin 2 (ADM2), a CGRP-related neuropeptide, that promotes tissue-protective ILC2 innate immune responses while limiting intestinal inflammation—revealing a neuropeptide-immune circuit for gut health.

Gut healing neuropeptide
Enteric neuron-derived ADM2 (CGRP-related) promotes tissue-protective immune responses while limiting gut inflammation—a new neuro-immune circuit

What the researchers found

Enteric neurons produce ADM2 (CGRP-related peptide). ADM2 promotes tissue-protective ILC2 responses. ADM2 limits intestinal inflammation. New neuro-immune circuit identified. Differential: proinflammatory vs tissue-protective regulation.

Why it matters

Understanding how gut neurons promote healing (not just inflammation) through CGRP-related peptides could lead to new treatments for IBD and other intestinal inflammatory conditions.

How the study worked

Neuro-immune circuit analysis in gut. ADM2 production by enteric neurons. ILC2 response characterization. Intestinal inflammation models.

What this study cannot tell us

Preclinical study. ILC2 biology is complex. Translation to human IBD needs validation. ADM2 receptor pharmacology not fully characterized.

How to read the evidence

Preclinical mechanistic study with neuro-immune circuit characterization.

When this study was published

Published in 2025.

The bigger picture

The CGRP peptide family has diverse roles: while CGRP itself drives migraine, its relative ADM2 promotes gut healing. Understanding this family's context-dependent functions enables more precise therapeutic targeting.

Questions still open

Could ADM2 agonists treat IBD?
Do anti-CGRP migraine drugs inadvertently affect gut ADM2 signaling?
Is ADM2 deficiency linked to IBD susceptibility?

Common questions

What is adrenomedullin 2?

ADM2 is a neuropeptide related to CGRP (the migraine peptide) produced by gut nerve cells. Unlike CGRP's role in pain, ADM2 promotes healing immune responses (ILC2 cells) while reducing gut inflammation. This discovery reveals a new brain-gut-immune connection.

Could this help with IBD?

Potentially. By promoting tissue-protective immune responses while limiting inflammation, ADM2 addresses the core problem in IBD. Drugs that boost ADM2 signaling—or mimic its effects on ILC2 cells—could become new treatments for Crohn's disease or ulcerative colitis.

Read the original research

CGRP-related neuropeptide adrenomedullin 2 promotes tissue-protective ILC2 responses and limits intestinal inflammation.

Nature immunology, 26(9), 1516-1526

View on PubMed ↗Publisher’s paper ↗

Citation

Uddin, Jazib; Yano, Hiroshi; Parkhurst, Christopher N; Zhang, Wen; Ahmed, Anees; Ribeiro de Godoy, Victoria; Wei, Qianru; Panchakshari, Rohit; Henninot, Antoine; Dasgupta, Surya; Gaudino, Stephen; Emanuel, Elizabeth R; Zeng, Peng; Miranda, Isabella; Hu, Elin; Tsou, Amy M; Artis, David. (2025). CGRP-related neuropeptide adrenomedullin 2 promotes tissue-protective ILC2 responses and limits intestinal inflammation.. Nature immunology, 26(9), 1516-1526. https://doi.org/10.1038/s41590-025-02243-2