Non-T cells are required for a poised Th17 phenotype and elevated IL-17 secretion by T cells from type 2 diabetes patients. (44.3)

Abstract

Abstract Type 2 Diabetes (T2D) has recently been identified as a chronic inflammatory disease with changes in immune cell function. Th17 cells and their major product, IL-17, have been implicated in multiple chronic inflammatory diseases. However, the relationship between Th17s and T2D has not been reported. Pro-inflammatory cytokines hyper-secreted by T2D patient monocytes promote Th17 activation. These data suggest a functional link between Th17s and monocytes in T2D. To identify such a link, we first showed that fresh ex vivo T cells from T2D patients have molecular signatures of Th17 cells. T2D T cells stimulated in the context of peripheral blood mononuclear cells (PBMCs) activated Th17 signature genes and elevated IL-17 secretion. In contrast, LPS stimulation of PBMCs from T2D patients failed to elevate IL-17 secretion, indicating that increased monocyte cytokine production, characteristic of T2D, does not further stimulate Th17 cells. Unexpectedly, continuous co-culture of T cells with the non-T cell fraction was required to maintain elevated Th17 function. These data indicate a crucial role for non-T cells in maintaining the Th17 phenotype and elevating IL-17 production in T2D. We conclude the interaction between T cells and non-T cells, most likely monocytes, promotes inflammation in T2D through previously unappreciated mechanisms.