Egr3 induces a Th17 response and systemic tissue inflammation by promoting the development of gamma delta T cells.

摘要

gammadelta T cells play an important role at both early and late stages of infection, helping to first shape the adaptive immune response and then restrain it. These innate-like cells are known to be one of the earliest producers of IL-17, and are capable of promoting a Th17 response in many settings. While the transcription factor Egr3 has been shown to attenuate a CD4 T cell response and promote anergy in settings of Thl activation, its role in Th17 differentiation has not yet been addressed. In pursuit of this, we discovered that Egr3 overexpression promotes thymic selection of 78 T cells and that this was associated with an increase in absolute numbers of peripheral gammadelta T cells as well as an increase in IL-17 production by CD4 T cells. We subsequently were able to show that Egr3-induced y8 T cells can directly skew CD4 T cells to a Th17 response. Egr3-induced gammadelta T cells are a diverse population, with variable gamma-chain usage and tissue homing similar to wildtype y5 T cells, only in greater numbers. Egr3 overexpressing mice are more susceptible to some induced inflammatory disease and spontaneous multi-organ pathology, suggesting Egr3- induced y5 T cells are functional in the mucosal compartment in addition to the periphery. Though Egr3 plays an indirect role in Th17 differentiation, it does so by promoting the development of a cell type which has both innate and adaptive characteristics and both protective and pathogenic potential .