Role of the gut microbiota in the development and function of lymphoid cells

Abstract

Mammals are colonized by large numbers of microorganisms, including trillions of bacteria, most of which live in the intestinal tract. These indigenous microorganisms that inhabit the body of humans and animals are referred collectively to as the microbiota. Accumulating evidence indicates that the microbiota regulates the development and/or function of different types of immune cells in the intestine. For example, the microbiota drives homeostatic, pathogenic, and regulatory T cell immune responses that contribute to tissue homeostasis, but also can promote disease. The gut microbes also facilitate IgA responses, which in turn regulate the composition and function of the gut microbiota. Thus, the reciprocal regulation of the gut microbiota and the host immune system may influence the balance between homeostasis and disease in the intestine.

Figure 1. Gut microbiota drive homeostatic, pathogenic and regulatory lymphocyte immunity

The gut microbiota directly or indirectly regulates the function of TCRγδ T cells. In turn, TCRγδ T cells regulate the microbiota through induction of the anti-microbial peptide RegIIIγ. The microbiota positively or negatively regulate the differentiation and/or function of RORγt⁺ ILCs. The microbiota stabilize the expression of RORγt⁺ in ILCs through induction of IL-7. The absence of microbiota-induced IL-7 signaling or the presence of IL-12 and IL-15 facilitates the conversion of RORγt⁺ ILCs into RORγt⁻ IFN-γ-producing pathogenic ILCs. Segmented filamentous bacteria (SFB) promote the differentiation of Th17 cells in the gut. Steady-state Th17 cells produce IL-17, IL-22 and IL-10 and may play an homeostatic role in the gut. IL-23, IL-12, IL-1β, TGF-β3 induce conversion of homeostatic Th17 cells towards pathogenic, IFN-γ-producing Th17 cells that facilitate intestinal inflammation. Certain subsets of commensal microbiota, such as Clostridium clusters XIVa and IV and Bacteroides fragilis, promote the development and functional maturation of Foxp3⁺Helios⁻ inducible Tregs. Foxp3⁺ iTregs suppress the expansion of Th17 cells as well as their conversion into IFN-γ-producing Th17 cells.