The characterization of thymus-derived natural Th17 cells and their response to inflammation. (108.9)

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 receptors -- IL-1R1 and IL-17RC -- that are expressed on nTh17 cells and play a role in their development and function. Development of nTh17 cells is hindered in the absence of IL1R1, and augmented in response to an increase of IL-1β. IL17-RC appears to be functional on nTh17 cells, in that it offers a way for the cells to regulate the levels of secreted IL-17A and IL-22.