Thymic self-reactivity selects for natural Th17 cells which can be distinguished by unique markers (143.49)

Abstract

Abstract CD4 T helper (Th) cells that secrete interleukin (IL)-17 (Th17) complement the function of Th1 and Th2 cells as a third effector lineage, with a distinct role in neutrophil recruitment necessary for extracellular pathogen clearance and the promotion of certain autoimmune conditions. We have previously demonstrated that natural Th17 (nTh17) cells develop within the thymus in a manner similar to that of natural T regulatory (nTreg) cells (Marks et al., Nat. Immunol. 2009), with activation in response to an increase of self-antigen due to tissue destruction and subsequent host protection via IL-22 secretion. In this study, we report microarray analysis of lymph node nTh17 cells, revealing specific patterns of gene expression compared to naïve, Th1, and nTreg cells. We identified 317 genes uniquely over- or under-expressed in nTh17 cells compared to controls. These results give new insights into the differences among naïve, nTreg, nTh17, and Th1 cells. We further identified two markers, IL-17RE and IL-17RC, that are expressed in nTh17 cells and not in the other subsets or in induced Th17 cells. Neither has been previously reported to be expressed in Th17 cells. IL-17RC appears to be functional in nTh17 cells, in that it offers a way for them to regulate the levels of secretion of IL-17A and IL-22. IL-17RC and IL-17RE could potentially be used as specific markers for natural Th17 cells.