CGRP-related peptide adrenomedullin 2 from gut neurons promotes protective ILC2 responses and limits intestinal inflammation
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.
Quick Facts
What This Study 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.
Key Numbers
How They Did This
Neuro-immune circuit analysis in gut. ADM2 production by enteric neurons. ILC2 response characterization. Intestinal inflammation models.
Why This Research 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.
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.
What This Study Doesn't Tell Us
Preclinical study. ILC2 biology is complex. Translation to human IBD needs validation. ADM2 receptor pharmacology not fully characterized.
Questions This Raises
- ?Could ADM2 agonists treat IBD?
- ?Do anti-CGRP migraine drugs inadvertently affect gut ADM2 signaling?
- ?Is ADM2 deficiency linked to IBD susceptibility?
Trust & Context
- Key Stat:
- Gut healing neuropeptide Enteric neuron-derived ADM2 (CGRP-related) promotes tissue-protective immune responses while limiting gut inflammation—a new neuro-immune circuit
- Evidence Grade:
- Preclinical mechanistic study with neuro-immune circuit characterization.
- Study Age:
- Published in 2025.
- Original Title:
- CGRP-related neuropeptide adrenomedullin 2 promotes tissue-protective ILC2 responses and limits intestinal inflammation.
- Published In:
- Nature immunology, 26(9), 1516-1526 (2025)
- Authors:
- Uddin, Jazib, Yano, Hiroshi(2), Parkhurst, Christopher N(2), 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
- Database ID:
- RPEP-13850
Evidence Hierarchy
Frequently Asked 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 More on RethinkPeptides
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Cite This Study
https://rethinkpeptides.com/research/RPEP-13850APA
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
MLA
Uddin, Jazib, et al. "CGRP-related neuropeptide adrenomedullin 2 promotes tissue-protective ILC2 responses and limits intestinal inflammation.." Nature immunology, 2025. https://doi.org/10.1038/s41590-025-02243-2
RethinkPeptides
RethinkPeptides Research Database. "CGRP-related neuropeptide adrenomedullin 2 promotes tissue-p..." RPEP-13850. Retrieved from https://rethinkpeptides.com/research/uddin-2025-cgrprelated-neuropeptide-adrenomedullin-2
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkPeptides research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.