γδ T-cell-deficient mice show alterations in mucin expression, glycosylation, and goblet cells but maintain an intact mucus layer

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 gamma delta T-cell-deficient (TCR delta(-) /(-)) mice to examine whether and how gamma delta T-cells modulate the properties of the intestinal mucus layer. Increased susceptibility of TCR delta (-/-) 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 TCR delta(-/-) mice compared with C57BL/ 6 wild-type (WT) mice. Addition of keratinocyte growth factor to small intestinal organoid cultures from TCR delta(-/-) 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 TCR delta(-/-) and WT mice, as measured in vivo. However, gamma delta 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 gamma delta 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.