The alarmin IL33 marks a thymocyte dependent shift in the makeup of cortical thymic epithelial cells

Functional competence in the adaptive immune system requires the generation of αβT-cells in the thymus, where thymic epithelial cells (TEC) drive thymocyte development. Roles for cortical thymic epithelial cells (cTEC) include the generation of CD4 + CD8 + thymocytes, and positive selection of cells capable of self-peptide/MHC recognition. Recently, we showed that, in the adult thymus, cTEC consist of two distinct subsets, Foxn1 + typical and Foxn1 - atypical cells. While typical cTEC regulate thymopoiesis through their expression of Psmb11 , Cxcl12 and Dll4 , the developmental requirements and properties of atypical cTEC remain undefined. Here, we show atypical cTEC downregulate the expression of multiple genes controlling antigen processing and presentation for positive selection including Psmb11 , Cd83 , Prss16 , and Ctsl . In addition, we show atypical cTEC acquire a distinct gene profile including the chemokines Ccl9 and Ccl11 together with the alarmin Il33 that plays an essential role in thymic repair following injury. Using precursor-product analysis and Cxcl12/Il33 dual reporter mice, we show Il33 -expressing atypical cTEC can be generated from typical cTEC that lack Il33 expression, a process which depends upon progression beyond the pre-TCR-mediated checkpoint. Together, these data define thymocyte-dependent changes in the adult cTEC compartment and suggest atypical cTEC may acquire functional properties that are distinct from their typical cTEC counterparts, including the possibility of acting as an additional source of IL33 in pathways of thymic regeneration.