γδ T-cell-deficient mice show alterations in mucin expression, glycosylation and goblet cells but maintain an intact mucus layer.
2014 (English)In: American Journal of Physiology - Gastrointestinal and Liver Physiology, ISSN 0193-1857, E-ISSN 1522-1547, Vol. 306, no 7, G582-G593 p.Article in journal (Refereed) Published
Intestinal homeostasis is maintained by a hierarchy of immune defences acting in concert to minimize contact between luminal microorganisms and the intestinal epithelial cell surface. The intestinal mucus layer, covering the gastrointestinal (GI) 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 sulphate (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 (SI) and colon of TCRδ(-/-) mice compared to C57BL/6 wt mice. Addition of keratinocyte growth factor (KGF) to small intestinal organoid cultures from TCRδ(-/-) mice showed a marked increase in crypt growth, and both goblet cell number and redistribution along the crypts. There was no apparent difference in the thickness or organisation 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 maintenance of mucosal homeostasis by regulating mucin expression and promoting goblet cell function in the small intestine.
Place, publisher, year, edition, pages
2014. Vol. 306, no 7, G582-G593 p.
Gastroenterology and Hepatology Physiology
IdentifiersURN: urn:nbn:se:uu:diva-220702DOI: 10.1152/ajpgi.00218.2013ISI: 000334674000004PubMedID: 24503767OAI: oai:DiVA.org:uu-220702DiVA: diva2:710385