title: γδ T-cell-deficient mice show alterations in mucin expression, glycosylation, and goblet cells but maintain an intact mucus layer.
abstract: Intestinal homeostasis is maintained by a hierarchy of immune defenses acting in concert to minimize contact between luminal microorganisms and the intestinal epithelial cell surface. The intestinal mucus layer, covering the gastrointestinal tract epithelial cells, contributes to mucosal homeostasis by limiting bacterial invasion. In this study, we used γδ T-cell-deficient (TCRδ(-/-)) mice to examine whether and how γδ T-cells modulate the properties of the intestinal mucus layer. Increased susceptibility of TCRδ(-/-) mice to dextran sodium sulfate (DSS)-induced colitis is associated with a reduced number of goblet cells. Alterations in the number of goblet cells and crypt lengths were observed in the small intestine and colon of TCRδ(-/-) mice compared with C57BL/6 wild-type (WT) mice. Addition of keratinocyte growth factor to small intestinal organoid cultures from TCRδ(-/-) mice showed a marked increase in crypt growth and in both goblet cell number and redistribution along the crypts. There was no apparent difference in the thickness or organization of the mucus layer between TCRδ(-/-) and WT mice, as measured in vivo. However, γδ T-cell deficiency led to reduced sialylated mucins in association with increased gene expression of gel-secreting Muc2 and membrane-bound mucins, including Muc13 and Muc17. Collectively, these data provide evidence that γδ T cells play an important role in the maintenance of mucosal homeostasis by regulating mucin expression and promoting goblet cell function in the small intestine.
authors: Gut Health and Food Safety Institute Strategic Programme, Institute of Food Research, Norwich, United Kingdom;
authors: Olivia I
authors: OI
authors: Kober
authors: David
authors: D
authors: Ahl
authors: Carmen
authors: C
authors: Pin
authors: Lena
authors: L
authors: Holm
authors: Simon R
authors: SR
authors: Carding
authors: Nathalie
authors: N
authors: Juge
mesh_terms: D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D003092:Colitis / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000378:metabolism; D005786:Gene Expression Regulation; D006031:Glycosylation; D020397:Goblet Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006706:Homeostasis; D018928:Immunity, Mucosal; D007421:Intestine, Small / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055262:Mucin-2 / Q000378:metabolism; D009077:Mucins / Q000235:genetics / Q000378:metabolism*; D009093:Mucus / Q000378:metabolism*; D009940:Organoids / Q000276:immunology / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency* / Q000235:genetics; D013997:Time Factors; D046509:Tissue Culture Techniques
chemical_list: D000954:Antigens, Surface; C063487:Ly64 protein, mouse; C524626:Muc2 protein, mouse; D055262:Mucin-2; D009077:Mucins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D004815:Epidermal Growth Factor; D016264:Dextran Sulfate
keywords: T cell receptor-γδ; intestinal intraepithelial lymphocytes; mouse mucin