γδ intraepithelial lymphocytes are essential mediators of host–microbial homeostasis at the intestinal mucosal surface

Abstract

The mammalian gastrointestinal tract harbors thousands of bacterial species that include symbionts as well as potential pathogens. The immune responses that limit access of these bacteria to underlying tissue remain poorly defined. Here we show that γδ intraepithelial lymphocytes (γδ IEL) of the small intestine produce innate antimicrobial factors in response to resident bacterial "pathobionts" that penetrate the intestinal epithelium. γδ IEL activation was dependent on epithelial cell-intrinsic MyD88, suggesting that epithelial cells supply microbe-dependent cues to γδ IEL. Finally, γδ T cells protect against invasion of intestinal tissues by resident bacteria specifically during the first few hours after bacterial encounter, indicating that γδ IEL occupy a unique temporal niche among intestinal immune defenses. Thus, γδ IEL detect the presence of invading bacteria through cross-talk with neighboring epithelial cells and are an essential component of the hierarchy of immune defenses that maintain homeostasis with the intestinal microbiota.antibacterial defense | mucosal immunity | microbiota

γδ T cells affect IL-4 production and B-cell tolerance

“…These findings with γδ T celldeficient mice have implications for humans because humans vary greatly with regard to γδ T-cell numbers and composition, due to genetic differences, during ontogeny, and as a consequence of diseases (5,6). As with mice, such variation might affect residual γδ T-cell function in humans, with consequences for antibody levels and other immune responses, and perhaps even host-microbial homeostasis (35).…”

Defining the nature of human γδ T cells: a biographical sketch of the highly empathetic

“…19,25,26 In the murine system, distinct subsets of cd T cells bearing specific pairs of the c and d TCR chains are targeted to particular epithelial locations during development such as the skin, lungs, uterus, vagina and tongue where they make up a significant portion of the local intraepithelial lymphocyte population and appear to respond to endogenous stress-induced antigens that have yet to be unambiguously identified. [27][28][29][30][31] For some of these special niche localized cd T…”

“…32,33 In the literature, these are often collectively called the 'non-Vd2' cd T cells. In addition to their role in maintaining immune homeostasis in the local microenvironment, 25 tissueassociated cd T cells, in both mice and men, play an important function in wound healing, removing distressed or transformed epithelial cells and subduing excessive inflammation. 19,26,[34][35][36][37][38][39] For example, in the gastrointestinal tract cd T cells play a non-redundant role in maintaining tolerance to food antigens as well as the intestinal flora.…”

Impact of the gut microbiota on enhancer accessibility in gut intraepithelial lymphocytes

“…IELs participate in immune surveillance, immune tolerance, wound repair, maintenance of gut barrier function, and protection from infectious agents (6). Given these roles, it is not surprising that considerable attention has been directed to how the microbiota shapes the IEL compartment (7,8), although the relationship between the microbiota and IELs is less well characterized than other components of the immune system. We also examined peripheral CD4 + and CD8 + T cells, reasoning that they may have transient exposures to products of the gut microbiota, can be sampled more readily than IELs, and would allow us to delineate extraintestinal epigenetic effects of the microbiota.…”