{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T08:30:06Z","timestamp":1788510606035,"version":"build-2803163510"},"reference-count":99,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T00:00:00Z","timestamp":1725235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH RO1","award":["DK129691-04"],"award-info":[{"award-number":["DK129691-04"]}]},{"name":"the American Neurogastroenterology and Motility Society (ANMS) Discovery Grants Program (NT)","award":["DK129691-04"],"award-info":[{"award-number":["DK129691-04"]}]},{"name":"the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN)","award":["DK129691-04"],"award-info":[{"award-number":["DK129691-04"]}]},{"name":"the Reckitt Mead Johnson Nutrition Research Young Investigator Development Award (NT)","award":["DK129691-04"],"award-info":[{"award-number":["DK129691-04"]}]},{"name":"the Irma and Norman Braman Endowment, and the Suzi and Scott Lustgarten Center Endowment","award":["DK129691-04"],"award-info":[{"award-number":["DK129691-04"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>A defining unique characteristic of the gut immune system is its ability to respond effectively to foreign pathogens while mitigating unnecessary inflammation. Intestinal macrophages serve as the cornerstone of this balancing act, acting uniquely as both the sword and shield in the gut microenvironment. The GI tract is densely innervated by the enteric nervous system (ENS), the intrinsic nervous system of the gut. Recent advances in sequencing technology have increasingly suggested neuroimmune crosstalk as a critical component for homeostasis both within the gut and in other tissues. Here, we systematically review the ENS\u2013macrophage axis. We focus on the pertinent molecules produced by the ENS, spotlight the mechanistic contributions of intestinal macrophages to gut homeostasis and inflammation, and discuss both existing and potential strategies that intestinal macrophages use to integrate signals from the ENS. This review aims to elucidate the complex molecular basis governing ENS\u2013macrophage signaling, highlighting their cooperative roles in sustaining intestinal health and immune equilibrium.<\/jats:p>","DOI":"10.3390\/biom14091103","type":"journal-article","created":{"date-parts":[[2024,9,2]],"date-time":"2024-09-02T12:54:42Z","timestamp":1725281682000},"page":"1103","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Neuroimmune Crossroads: The Interplay of the Enteric Nervous System and Intestinal Macrophages in Gut Homeostasis and Disease"],"prefix":"10.3390","volume":"14","author":[{"given":"Meng","family":"Lou","sequence":"first","affiliation":[{"name":"Department of Pediatrics, The Children\u2019s Hospital of Philadelphia Research Institute, Abramson Research Center and Department of Pediatrics, Pearlman School of Medicine at the University of Pennsylvania, 3615 Civic Center Blvd, Philadelphia, PA 19004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3282-1765","authenticated-orcid":false,"given":"Robert O.","family":"Heuckeroth","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Children\u2019s Hospital of Philadelphia Research Institute, Abramson Research Center and Department of Pediatrics, Pearlman School of Medicine at the University of Pennsylvania, 3615 Civic Center Blvd, Philadelphia, PA 19004, USA"},{"name":"Division of Gastroenterology, Nutrition and Hepatology, The Children\u2019s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9507-4103","authenticated-orcid":false,"given":"Naomi E. Butler","family":"Tjaden","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, The Children\u2019s Hospital of Philadelphia Research Institute, Abramson Research Center and Department of Pediatrics, Pearlman School of Medicine at the University of Pennsylvania, 3615 Civic Center Blvd, Philadelphia, PA 19004, USA"},{"name":"Division of Gastroenterology, Nutrition and Hepatology, The Children\u2019s Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2308511120","DOI":"10.1073\/pnas.2308511120","article-title":"The total mass, number, and distribution of immune cells in the human body","volume":"120","author":"Sender","year":"2023","journal-title":"Proc. Natl. Acad. Sci. 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