Aryl hydrocarbon receptor: a molecular link between postnatal lymphoid follicle formation and diet

Abstract

Intestinal homeostasis results from a complex mutualism between gut microbiota and host cells. Defining the molecular network regulating such mutualism is currently of increasing interest, as its deregulation is reported to lead to increased susceptibility to infections, chronic inflammatory bowel diseases and cancer. Until now, the focus has been on the mechanism, by which the composition of indigenous microbiota shapes the immune system. In a recent study, we have shown that dietary compounds have also the ability to affect innate immune system. This regulation involves aryl hydrocarbon receptor (AhR), a sensor of plant-derived phytochemicals, which mediates the maintenance of Retinoic acid related orphan receptor γ t-expressing innate lymphoid cells (RORγt(+) ILC) in the gut and consequently formation of postnatal lymphoid follicles. Thus, AhR represents the first evidence of a molecular link between diet and immunity at intestinal mucosal surfaces.

Figures

Figure 1. Aryl Hydrocarbon Receptor (AhR) activity in RORγt+ ILC is essential for the first step of lymphoid follicle formation in the gut. Intestinal lymphoid follicles such as cryptopatches (CP) appear early after birth via the recruitment and the expansion of RORγt+ ILC at site. This step is independent of the presence of the indigenous microbiota in the gut. After CP development, invading microbiota drives some of them to further evolve into isolated lymphoid follicles (ILF) via the recruitment of plasma cells. Importantly, RORγt+ ILC expansion seems to be dependent on external factors such as nutrients. RORγt+ ILC, in particular the CD4-negative cell subset, are able to sense variation in phytochemical compound in the diet via the AhR. Activation of AhR induces upregulation of Kit and potentially Notch2 and IL-7R on RORγt+ ILC, supporting their maintenance. In Ahr-deficient mice, CD4- RORγt+ ILC cannot survive and expand leading to a lack of intestinal lymphoid follicle formation.