Reciprocal Interactions between Commensal Bacteria and γδ Intraepithelial Lymphocytes during Mucosal Injury

The intestinal mucosal surface is in direct contact with a vast beneficial microbiota. The symbiotic nature of this relationship is threatened when the surface epithelium is injured, yet little is known about how mucosal surfaces maintain homeostasis with commensal microbes following damage. gamma delta Intraepithelial lymphocytes (gamma delta IEL) reside tit the grit epithelial surface, where they stimulate mucosal healing following acute injury. A genome-wide analysis of the gamma delta IEL response to dextran sulfate sodium-induced colonic damage revealed induction of a complex transcriptional program, including coordinate regulation of cytoprotective, immunomodulatory, and antibacterial factors. Studies in germfree mice demonstrated that commensal microbiota regulate key components of this transcriptional program, thus revealing a dialogue between commensal bacteria and gamma delta IEL in injured epithelia. Analysis of TCR delta-deficient mice indicated that gamma delta T cells are essential for controlling mucosal penetration of commensal bacteria immediately following dextran sulfate sodium-induced damage, suggesting that a key function of gamma delta IEL is to maintain host-microbial homeostasis following acute mucosal injury. Taken together, these findings disclose a reciprocal relationship between gamma delta T cells and intestinal microbiota that promotes beneficial host-microbial relationships in the intestine. The Journal of Immunology, 2009, 182: 3047-3054.