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RORγt is a nuclear hormone receptor that has followed an exponential success carrier. Its modest origins as an orphan receptor cloned from human pancreas blossomed within 15 years into a critical regulator of anti-microbial immunity and a major target in the fight against inflammatory pathologies. Here, I review its role as a transcription factor required for the generation of type 3 lymphoid cells, which induce the development of lymphoid tissues, provide resistance of epithelial stem cells to injury, maintain homeostasis with the symbiotic microbiota, orchestrate defense against extracellular microbes, and regulate allergic responses. RORγt is also an intriguing molecule that is regulated by the circadian rhythm and includes cholesterol metabolites as ligands. RORγt therefore links anti-microbial immunity with circadian rhythms and steroids, the logic of which remains to be understood.

RORγt, a multitask nuclear receptor at mucosal surfaces