ITK is a key signaling mediator downstream of TcR, mediating T cell positive selection, innate T cell and CD4+ Th2/Th17 differentiation. Here we show that ITK also negatively tunes IL-2-induced expansion of Foxp3+ regulatory T cells (Treg). In vivo, Treg abundance is inversely correlated with ITK expression, and iTreg development is inversely dependent on ITK kinase activity. While Treg development normally requires both hematopoietic and thymic MHC class 2 (MHC2) expression, the absence of ITK allows Treg development with MHC2 expression in either compartment with preference for selection by thymic MHC2, suggesting a gatekeeper role of ITK in ensuring that only Treg cells selected by both thymic and hematopoietic MHC2 survive selection. Although ITK suppresses Treg development and is not required for maintenance of NRP1+ natural Treg cells in the periphery, it is indispensable for Treg functional suppression of naïve CD4+ T cell-induced colitis in Rag−/− recipients. ITK thus regulates the development and function of Treg cells.

There is mixed evidence for the utility of PMRT with immediate autologous abdominal wall breast reconstruction. Further investigation requires prospective studies with collaboration among surgical oncologists, radiation oncologists, and plastic surgeons.

Itk−/− mice exhibit defects in activation, development and function of CD4+ and CD8+ T cells and iNKT cells. These and other defects in these mice make it difficult to uncouple the developmental versus functional requirement of Itk signaling. Here we report an allele sensitive mutant of Itk (Itkas) whose catalytic activity can be selectively inhibited by analogs of the PP1 kinase inhibitor. We show that Itkas behaves like WT Itk in the absence of the inhibitor and can rescue the development of Itk−/− T cells in mice. Using this mutant, we show that Itk activity is required not only for Th2, Th17 and iNKT cell cytokine production, but also surprisingly, for Th1 cytokine production. This work has important implications for understanding the role of Itk signaling in development vs. function of iNKT cells, Th1, Th2 and Th17.

Macular GCA using SD-OCT can be used to complement visual field assessment and brain MRI findings during evaluation of patients with pituitary tumor.