Chikkamenahalli Lakshmikanth L, Jessen Erik, Bernard Cheryl E, Ip W K Eddie, Breen-Lyles Margaret, Cipriani Gianluca, Pullapantula Suraj R, Li Ying, AlAsfoor Shefaa, Wilson Laura, Koch Kenneth L, Kuo Braden, Shulman Robert J, Chumpitazi Bruno P, McKenzie Travis J, Kellogg Todd A, Tonascia James, Hamilton Frank A, Sarosiek Irene, McCallum Richard, Parkman Henry P, Pasricha Pankaj J, Abell Thomas L, Farrugia Gianrico, Dasari Surendra, Grover Madhusudan
Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA.
Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
iScience. 2024 Jan 23;27(3):108991. doi: 10.1016/j.isci.2024.108991. eCollection 2024 Mar 15.
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.
胃肠道免疫细胞，尤其是肌层巨噬细胞（MM）与肠神经系统相互作用并影响胃肠动力。在此，我们确定了人类胃肌免疫组及其在特发性胃轻瘫（IG）患者中的变化。对从20名受试者的胃组织中获取的26,000个CD45细胞进行了单细胞测序。我们证实了11个免疫细胞簇，其中T细胞最为丰富，其次是髓系细胞。IG患者和对照组中属于这11个簇的细胞比例相似。然而，11个簇中的9个显示出578 - 11,429个差异表达基因。在IG患者中，MM的组织保护基因和小胶质细胞基因表达降低，单核细胞转运和基质激活基因的表达增加。此外，在IG患者中，参与组织驻留巨噬细胞激活的IL12介导的JAK - STAT信号通路以及参与单核细胞趋化作用的Eph - ephrin信号通路被上调。IG患者中单核细胞样细胞更为丰富。这些数据进一步将免疫失调与胃轻瘫的病理生理学联系起来。
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