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.

Regulatory immune cells in regulation of intestinal inflammatory response to microbiota

“…33 In addition, TCRγδ + T cell-deficient mice showed an increase in susceptibility to DSS-induced colitis because of reduced mucin expression and impaired goblet cell function. 34 For immune regulation of intestinal mucosa, TCRγδ + T cells could increase the production of TGF-β and IL-10 to perform their suppressive function in intestinal inflammation. 35,36 CD8αα + TCRαβ + IELs have also been reported that provide the protective effects for intestinal mucosa by expressing some immune regulatory molecules, such as TGF-β, lymphocyte activation gene 3, and killer cell immunoglobulin-like receptors.…”

Sentinels at the Frontline: the Role of Intraepithelial Lymphocytes in Inflammatory Bowel Disease

“…Further identification of the IEL subpopulation(s) responsible for the alterations in goblet cell physiology would be of particular interest since γδ T cells were shown to influence goblet cell number and mucin production and glycosylation. [71] Pro-inflammatory cytokine production by IELs may impair the protective mucus barrier and contribute to the exacerbation of disease. These findings are consistent with the reduced goblet cell number and altered mucin production observed in Crohn’s disease and ulcerative colitis.…”

The effect of coenzyme Q10 on age-related changes of the distal colon mucosa of male albino rats

“…Some researchers stated that deterioration in intestinal barrier functions and alteration of intestinal microbiota occurred with aging. These might permit increased systemic absorption of intestinal luminal antigens and lead to inflammation [21,22].…”

“…Mucus is continuously secreted by goblet cells into the GIT lumen and acts as a barrier that contributes to mucosal homeostasis by limiting bacterial invasion. The number and function of goblet cells are modulated by this invasion [20,21].…”