Adaptation of innate lymphoid cells to nutrient deprivation promotes type 2 barrier immunity

Survival of the host relies on the establishment of a functional barrier immune defense that must be maintained in fluctuating states of food availability. Vitamin A deficiency is one of the most common nutrient deficiencies associated with defects in adaptive immune responses and profound immunosuppression. We found that vitamin A deficiency results in impaired immunity against bacterial infection accompanied by a fundamental decrease in IL-22 producing type 3 innate lymphoid cells (ILC3). Paradoxically deprivation of vitamin A results in a profound expansion of IL-13 producing ILC2 that confer enhanced type 2 immunity to helminth infections. Such changes in intestinal barrier immunity correlate with altered metabolic requirements of intestinal ILC2, suggesting a metabolic adaptation of ILC mediated barrier immunity. Thus the essential nutrient vitamin A regulates an inverse balance between intestinal ILC subsets promoting ILC3 while directly suppressing IL-13 producing ILC2.  These results reveal ILC as primary sensors of the nutritional status and signify a powerful adaptation of the immune system during malnutrition to promote host survival in the face of limited nutritional availability.