Single cell atlas of human gastric muscle immune cells and macrophage-driven changes in idiopathic gastroparesis.

Autor:	Chikkamenahalli LL; Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA., Jessen E; Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA., Bernard CE; Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA., Ip WKE; Department of Immunology, Mayo Clinic, Rochester, MN, USA., Breen-Lyles M; Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA., Cipriani G; Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA., Pullapantula SR; Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA., Li Y; Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA., AlAsfoor S; Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA., Wilson L; Johns Hopkins University Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA., Koch KL; Wake Forest University, Winston-Salem, NC, USA., Kuo B; Massachusetts General Hospital, Boston, MA, USA., Shulman RJ; Baylor College of Medicine, Houston, TX, USA., Chumpitazi BP; Duke University, Durham, NC, USA., McKenzie TJ; Department of Surgery, Mayo Clinic, Rochester, MN, USA., Kellogg TA; Department of Surgery, Mayo Clinic, Rochester, MN, USA., Tonascia J; Johns Hopkins University Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA., Hamilton FA; National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA., Sarosiek I; Texas Tech University Health Sciences Center, El Paso, TX, USA., McCallum R; Texas Tech University Health Sciences Center, El Paso, TX, USA., Parkman HP; Temple University, Philadelphia, PA, USA., Pasricha PJ; Mayo Clinic, Scottsdale, AZ, USA., Abell TL; University of Louisville, Louisville, KY, USA., Farrugia G; Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA., Dasari S; Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA., Grover M; Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA.
Jazyk:	angličtina
Zdroj:	IScience [iScience] 2024 Jan 23; Vol. 27 (3), pp. 108991. Date of Electronic Publication: 2024 Jan 23 (Print Publication: 2024).
DOI:	10.1016/j.isci.2024.108991
Abstrakt:	Gastrointestinal immune cells, particularly muscularis macrophages (MM) interact with the enteric nervous system and influence gastrointestinal motility. Here we determine the human gastric muscle immunome and its changes in patients with idiopathic gastroparesis (IG). Single cell sequencing was performed on 26,000 CD45 + cells obtained from the gastric tissue of 20 subjects. We demonstrate 11 immune cell clusters with T cells being most abundant followed by myeloid cells. The proportions of cells belonging to the 11 clusters were similar between IG and controls. However, 9/11 clusters showed 578-11,429 differentially expressed genes. In IG, MM had decreased expression of tissue-protective and microglial genes and increased the expression of monocyte trafficking and stromal activating genes. Furthermore, in IG, IL12 mediated JAK-STAT signaling involved in the activation of tissue-resident macrophages and Eph-ephrin signaling involved in monocyte chemotaxis were upregulated. Patients with IG had a greater abundance of monocyte-like cells. These data further link immune dysregulation to the pathophysiology of gastroparesis. Competing Interests: Madhusudan Grover has received investigator-initiated grant funding from Takeda pharmaceuticals and clinical trial funding from Alexza and Donga pharmaceuticals. He serves as a consultant for Alfasigma, Ardelyx and Evoke pharmaceuticals. Bruno P. Chumpitazi receives research funding from Cairn Diagnostics, is a consultant for Ironwood Pharmaceuticals, and receives royalties from the Rome Foundation. These entities did not support the presented work. No disclosures for other co-authors. (© 2024 The Author(s).)
Databáze:	MEDLINE
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