Role of the gut microbiota in immune regulation

Innate lymphoid cells (ILC) are a type of specialized innate immune cells. They are a group of lymphocytes that do not have antigen-specific receptors⁶ and have been recently identified and divided into three groups based on the type of secreted cytokines: ILC1 that produces interferon gamma (IFN-γ) and similar to T-helper cells Th1, ILC2 similar to Th2 (IL-5, IL-6, IL-13) and ILC3 similar to Th17 (IL-17, IL-22). The studies on the microbiota and ILCs, currently booming, also show that the microbiota seems to be necessary to the development and functions of ILCs, especially Group 3 ILCs. ILC3 are the main intestinal source of IL-22, a cytokine that is key to the production of antimicrobial proteins.⁶

ADAPTIVE IMMUNITY

The gut microbiota is also core to the activation of the adaptive response. At the T-cell level, it induces the maturation of naïve T-cells into IL-17-producing cells (Th17) which stimulate the production of antimicrobial peptides by the intestinal epithelium. It also promotes the synthesis of some CD4+ regulatory T-cells (Treg) that have an anti-inflammatory action. Finally, it contributes to the development of secondary lymphoid tissues in the intestines where T-cells are stored. Regarding B-cells, the gut microbiota ensures, through IL-17, that secretory IgA produced by B-cells crosses through the intestinal mucosa to join the lumen and neutralize harmful toxins and bacteria. The combination of strong IgA responses and pro-inflammatory (Th17) and anti-inflammatory (Treg) responses from T-cells create a state of physiological inflammation controlled by the gut microbiota.^3,5