Innate lymphoid cells link gut microbes with mucosal T cell immunity

Abstract

Despite continuous exposure to trillions of microbes, the intestinal immune system protects the mucosa by balancing barrier protection, tolerance, and immunity. As both sentinel and effector, the mucosal innate immune system plays a central role in coordinating these responses. By integrating signals from the intestinal microbiota, mononuclear phagocytes (MNPs) serve as a critical link in regulating effector functions of group 3 innate lymphoid cells (ILC3s). Our recent work identified the role for MNP production of the IBD-linked protein TNF-like ligand 1A (TL1A) in modulating microbial regulation of ILC3 barrier immunity. These findings highlight a broader role for ILC3s in local control of T cell immunity and their potential role in the pathogenesis and treatment of inflammatory disease.

Keywords: Innate lymphoid cells; OX40L; TL1A; inflammatory bowel diseases.

Figure 1.

Microbial induction of TL1A regulates ILC3 barrier immunity. Mucosal-associated microbiota are sensed by intestinal CX3CR1+ MNPs and induce expression of cytokines and TL1A. TL1A enhances ILC3 production of effector cytokines, including IL-22, promoting mucosal healing associated with acute colitis. TL1A also induces MHCII+ ILC3 expression of the co-stimulatory molecule OX40L which can support mucosal inflammatory T cells. The broader impact of ILC3 expression of OX40L in regulating microbe-specific mucosal T cell immunity remains to be determined.