CD74 Signaling Links Inflammation to Intestinal Epithelial Cell Regeneration and Promotes Mucosal HealingSummary
| Autor: | Shannon Moonah, Koji Watanabe, Swagata Ghosh, Nona M. Jiang, Richard Bucala, Mahmut Parlak, Laura Farr |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
WT wild type CD74 Biopsy medicine.medical_treatment EphB ephrin type B receptor TNBS trinitrobenzene sulfonic acid Datasets as Topic CD74 cluster of differentiation 74 PI3K phosphatidylinositol-3-kinase Inflammatory bowel disease MIF macrophage migration inhibitory factor Mice 0302 clinical medicine Crohn Disease ERK extracellular signal-regulated kinase GST Glutathione S-transferase DSS dextran sodium sulfate Intestinal Mucosa Bone Marrow Transplantation Original Research MIF Receptor Proliferation Pathways Mice Knockout TNF tumor necrosis factor IBD inflammatory bowel disease Entamoeba histolytica Gastroenterology HBSS Hank’s buffered salt solution Colitis Intramolecular Oxidoreductases Editorial Cytokine 030211 gastroenterology & hepatology TEV Tobacco Etch Virus medicine.symptom Signal Transduction Primary Cell Culture IBD Inflammation Biology Permeability 03 medical and health sciences Immune system Cell Line Tumor medicine Animals Humans Regeneration lcsh:RC799-869 Macrophage Migration-Inhibitory Factors Protein kinase B Transplantation Chimera Hepatology Gene Expression Profiling Histocompatibility Antigens Class II Epithelial Cells medicine.disease Antigens Differentiation B-Lymphocyte Disease Models Animal 030104 developmental biology MBP maltose binding protein Akt protein kinase B Cancer research Colitis Ulcerative Macrophage migration inhibitory factor lcsh:Diseases of the digestive system. Gastroenterology Repair |
| Zdroj: | Cellular and Molecular Gastroenterology and Hepatology, Vol 10, Iss 1, Pp 101-112 (2020) Cellular and Molecular Gastroenterology and Hepatology |
| Popis: | Background & Aims The inflammatory response to intestinal damage promotes healing through mechanisms that are incompletely understood. Gene expression of cluster of differentiation 74 (CD74), the receptor for cytokine macrophage migration inhibitory factor, is increased in patients with inflammatory bowel disease (IBD), however, the role of CD74 signaling in intestinal inflammation remains poorly understood. The aim of this study was to determine the functional role of CD74 signaling in intestinal inflammation. Methods We studied the characteristics of CD74 protein expression in human IBD and experimental colitis. The functional role of CD74 signaling in the intestine was investigated using cellular models; wild-type, CD74-/-, and bone marrow chimera mice; neutralizing anti-CD74 antibodies; flow cytometry; immunohistochemistry; immunofluorescence; immunoblotting; and clustered regularly interspaced short palindromic repeats and associated protein 9 technology. Results In IBD patients and experimental colitis, CD74-receptor protein expression was increased in inflamed intestinal tissue, prominently in the crypt epithelial cells. By using distinct but complementary chemical and non–chemically induced mouse models of colitis with genetic and antibody neutralization approaches, we found that CD74 signaling was necessary for gut repair. Mechanistically, we found that the macrophage migration inhibitory factor cytokine, which also is increased in colitis, stimulated the CD74 receptor, enhancing intestinal epithelial cell proliferation through activation of the protein kinase B and the extracellular signal-regulated kinase pathways. Our data also suggest that CD74 signaling in immune cells was not essential for mucosal healing. Conclusions CD74 signaling is strongly activated during intestinal inflammation and protects the host by promoting epithelial cell regeneration, healing, and maintaining mucosal barrier integrity. Enhancing the CD74 pathway may represent a unique therapeutic strategy for promoting healing in IBD. Graphical abstract |
| Databáze: | OpenAIRE |
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