THE EFFECT OF THE DIET ON THE DEVELOPMENT AND HOMEOSTASIS OF INNATE LYMPHOID CELLS (ILCS)

ILCs are recently discovered heterogeneous populations of lymphocytes found mostly in the mucosal tissues that display several important functions, including regulation of intestinal homeostasis. ILCs appear to be primordial precursor of T cells, as ILCs lack an Ag-specific receptor, but closely resemble effector CD4⁺ T cell subsets in terms of cytokine profiles and transcription factors. The precise role of commensal microbiota and dietary Ags in the intestinal immune homeostasis of ILCs is poorly understood. We found that only a minor fraction of Type 3 ILCs was partially depleted in germ-free (GF) mice. By contrast, Ag-free (AF) mice, which are devoid of both commensal bacteria and dietary Ags, were found to have a dramatically elevated number of Type2 ILCs, which produced considerably higher amounts of T_H2-associated effector cytokines than Type2 ILCs in conventional and GF mice. Moreover, Type3 ILCs in AF mice were severely depleted compared to that in conventional and GF mice. Accordingly, while the basal proliferation rate of Type 3 ILCs was similar in conventional and GF mice, it was minimal in AF mice. Various experiments confirmed the role of dietary antigens in modulating Type3 ILCs and Type2 ILCs. We are currently investigating whether the dietary Ags and/or various components of the diet directly or indirectly affect development, homeostasis and function of ILC subsets.