Reconciling the spectrum of RORγt ⁺ antigen-presenting cells

Three recent contemporaneously published papers ^1–3 showed that antigen-presenting cells (APC) expressing the nuclear receptor RORγt instruct peripheral regulatory T (pTreg) cell differentiation and establish tolerance to the gut microbiota. These studies identified a spectrum of RORγt ⁺ APCs, distinct from dendritic cells, that included type 3 innate lymphoid cells (ILC3s) as well as novel APC types. Given the discordant conclusions as to the nature of the pTreg-inducing APC and the divergent nomenclature used in these three studies, there is a clear need to reconcile these analyses and the identity of the cell types described. Our reanalysis of the single cell RNA-seq data from these studies revealed the presence of four distinct subsets of non-ILC3 RORγt ⁺ APCs, present in all three datasets reported, and confirmed expression of Itgb8, the critical factor for RORγt ⁺ APC mediated pTreg induction, in cells synonymous with the non-Aire expressing Thetis cell subset, TC IV.