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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Adaptive Immunity, Animals, Cells, Cultured, Coculture Techniques, Colitis, Colon, Disease Models, Animal, Feedback, Physiological, Genes, T-Cell Receptor alpha, Homeodomain Proteins, Immunity, Innate, Inflammation Mediators, Intestinal Mucosa, Mice, Mice, Inbred C57BL, Mice, Knockout, Mucin-1, Permeability, Signal Transduction, Th1 Cells, Th17 Cells, Th2 Cells.
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Does the membrane-bound mucin Muc1 regulate T helper 17-cell responses and colitis in mice? Context: T helper (Th) 17 cells produce the effector cytokine interleukin (IL)-17, along with IL-22, which stimulates colonic epithelial cells to produce a membrane-bound mucin, Muc1. Muc1 is a component of the colonic mucus, which functions as a lubricant and a physiologic barrier between luminal contents and mucosal surface. The gene MUC1 has been associated with susceptibility to inflammatory bowel disease; we investigated the role of Muc1 in development of colitis in mice. Muc1 and RAG1 were disrupted in mice (Muc/RAG double knockout mice); Th1-mediated colitis was induced by intravenous injection of CD4(+)CD45RB(high) T cells. We also studied Th2-mediated colitis using mice with disruptions in Muc1 and T-cell receptor α chain (Muc/TCR double knockout mice). Muc1 deficiency led to the development of more severe forms of Th1- and Th2-induced colitis than controls. Loss of Muc1 increased colonic permeability and the Th17-cell, but not Th2 or Th1 cell, response in the inflamed colon. Loss of Muc1 also promoted expansion of an innate lymphoid cell population (Lin(-) ckit(-) Thy1(+) Sca1(+)) that produces IL-17. The expansion of Th17 adaptive immune cells and innate lymphoid cells required the commensal microbiota.
assistant
Muc1, which is up-regulated by Th17 signaling, functions in a negative feedback pathway that prevents an excessive Th17 cell response in inflamed colons of mice. Disruption of this negative feedback pathway, perhaps by variants in Muc1, might contribute to inflammatory bowel disease in patients. Final Decision: yes