Tissue-resident memory Th17 cells maintain stable fungal commensalism in the oral mucosa

Keeping a stable equilibrium between the host and commensal microbes to which we are constantly exposed, poses a major challenge for the immune system. The host mechanisms that regulate homeostasis of the microbiota to prevent infection and inflammatory disorders are not fully understood. Here, we provide evidence that CD4⁺ tissue-resident memory T (T_RM) cells act as central players in this process. Using a murine model of C. albicans commensalism we show that IL-17 producing CD69⁺CD103⁺CD4⁺ memory T cells persist in the colonized tissue long-term and independently of circulatory supplies. Consistent with the requirement of Th17 cells for limiting fungal growth, IL-17-producing T_RM cells in the mucosa were sufficient to maintain prolonged colonization, while circulatory T cells were dispensable. Although T_RM cells were first proposed to protect from pathogens causing recurrent acute infections, our results support a central function of T_RM cells in the maintenance of commensalism.