Figure 1 – Tissue resident memory signals regulated by the microbiota.

Trms reside in tissues and are directed by signals in their local environment. The microbiota is one of the dominant factors controlling the barrier tissue environment and microbiota-derived signals may be important Trm survival. A) Microbiota derived SCFAs direct T cell metabolism toward Oxidative Phosphorylation (OxPhos) and Fatty Acid Oxidation (FAO) that benefit long-term survival. B) Microbiota controls the production of Retinoic Acid from Vitamin A, which via activation of the transcription factor Rarα activates expression of the chemokine receptor CCR9 and the integrin α4β7 which guide T cells back to the intestine. C) Microbiota-induced IFNγ and dendritic cell activation can increase IL-7 and IL-15 production, which activates anti-apoptotic genes (Bcl-2, Bcl-XL). D) MDR1 and CAR protect T cells against bile acid induced toxicity allowing for survival in the small intestine and decrease inflammation via increasing IL-10 and decreasing TNFα.