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

Lakshmikanth L Chikkamenahalli; Erik Jessen; Cheryl E Bernard; W K Eddie Ip; Margaret Breen-Lyles; Gianluca Cipriani; Suraj R Pullapantula; Ying Li; Shefaa AlAsfoor; Laura Wilson; Kenneth L Koch; Braden Kuo; Robert J Shulman; Bruno P Chumpitazi; Travis J McKenzie; Todd A Kellogg; James Tonascia; Frank A Hamilton; Irene Sarosiek; Richard McCallum; Henry P Parkman; Pankaj J Pasricha; Thomas L Abell; Gianrico Farrugia; Surendra Dasari; Madhusudan Grover; NIDDK Gastroparesis Clinical Research Consortium (GpCRC)

doi:10.1016/j.isci.2024.108991

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

iScience. 2024 Jan 23;27(3):108991. doi: 10.1016/j.isci.2024.108991. eCollection 2024 Mar 15.

Authors

Lakshmikanth L Chikkamenahalli¹, Erik Jessen², Cheryl E Bernard¹, W K Eddie Ip³, Margaret Breen-Lyles¹, Gianluca Cipriani¹, Suraj R Pullapantula¹, Ying Li², Shefaa AlAsfoor¹, Laura Wilson⁴, Kenneth L Koch⁵, Braden Kuo⁶, Robert J Shulman⁷, Bruno P Chumpitazi⁸, Travis J McKenzie⁹, Todd A Kellogg⁹, James Tonascia⁴, Frank A Hamilton¹⁰, Irene Sarosiek¹¹, Richard McCallum¹¹, Henry P Parkman¹², Pankaj J Pasricha¹³, Thomas L Abell¹⁴, Gianrico Farrugia¹, Surendra Dasari², Madhusudan Grover¹; NIDDK Gastroparesis Clinical Research Consortium (GpCRC)

Affiliations

¹ Division of Gastroenterology and Hepatology, Enteric Neuroscience Program, Mayo Clinic, Rochester, MN, USA.
² Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA.
³ Department of Immunology, Mayo Clinic, Rochester, MN, USA.
⁴ Johns Hopkins University Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
⁵ Wake Forest University, Winston-Salem, NC, USA.
⁶ Massachusetts General Hospital, Boston, MA, USA.
⁷ Baylor College of Medicine, Houston, TX, USA.
⁸ Duke University, Durham, NC, USA.
⁹ Department of Surgery, Mayo Clinic, Rochester, MN, USA.
¹⁰ National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD, USA.
¹¹ Texas Tech University Health Sciences Center, El Paso, TX, USA.
¹² Temple University, Philadelphia, PA, USA.
¹³ Mayo Clinic, Scottsdale, AZ, USA.
¹⁴ University of Louisville, Louisville, KY, USA.

Abstract

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.

Keywords: Gastroenterology; Immunology; Transcriptomics.

Abstract

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