Th17 play a central role in autoimmune inflammatory responses. Th1 are also necessary for autoimmune disease development. The interplay of Th1 signals and how they coordinate with Th17 during inflammatory disease pathogenesis are incompletely understood. In this study, by adding Stat4 deficiency to Stat6/T-bet double knockout, we further dissected the role of Stat4 in Th1 development and coliti...

Transcriptional regulatory networks direct the development of specialized cell types. The transcription factors signal tranducer and activator of transcription 4 (Stat4) and T-bet are required for the interleukin-12 (IL-12)-stimulated development of T helper 1 (Th1) cells, although the hierarchy of activity by these factors has not been clearly defined. In this report, we show that these factor...

IgG2a is known to be the most efficient antibody isotype for viral clearance. Here, we demonstrate a unique pathway of B-cell activation, leading to IgG2a production, and involving synergistic stimulation via B-cell antigen receptors, toll-like receptor 7 (TLR7), and IFNγ receptors on B cells. This synergistic stimulation leads to induction of T-box transcription factor T-bet expression in B ce...

Abstract Adoptive transfer of T cells modified with a chimeric antigen receptor (CAR) are highly effective in patients hematologic malignancies. However, many relapse and CAR have shown minimal efficacy against solid tumors. Our lab others that standard designs fail to promote differentiation into canonical cell subsets. generate both type-1 type-2 cytokines simultaneously, challenging the trad...

While studying Th responses induced by cardiac transplantation, we observed that mice deficient in the Th1 transcription factor T-bet (T-bet(-/-)) mount both Th1 and Th17 responses, whereas wild-type recipients mount only Th1 responses. Cells producing both IFN-gamma and IL-17 were readily detectable within the rejecting graft of T-bet(-/-) recipients, but were absent from the spleen, indicatin...

Objectives. Th1 cells have been implicated as the causal agents in the pathogenesis of autoimmunity. SLE represents the classical prototype of systemic autoimmune disease. Copy number variations (CNVs) have been discovered to have phenotypic consequences and associate with various types of diseases. The current study aims to explore a possible association between CNVs of Th1 cell-related genes ...

Mice with a targeted deletion of the T-bet gene exhibit spontaneous airway hyperresponsiveness (AHR), airway inflammation, enhanced recovery of T(h)2 cytokines from bronchoalveolar lavage fluid, sub-epithelial collagen deposition and myofibroblast transformation. Here we analyze the mechanisms responsible for the chronic airway remodeling observed in these mice. CD4+ T cells isolated from the l...

The T-box transcription factor T-bet is an important regulator of IFN-gamma production in all cell types and is considered to be essential for the generation of CD4 Th1 T cells. IFN-gamma in turn plays a critical role in immunity to many infectious agents. In this study, we demonstrate that T-bet is not required for host resistance to primary Listeria monocytogenes (LM) infection. In the innate...

Peripheral natural killer (NK) cells upregulate T-bet and downregulate Eomes, the key transcription factors regulating NK cell maturation and function during the last maturation steps toward terminally differentiated effector cells. During this process, NK cells acquire killer immunoglobulin-like receptors (KIR) and effector functions, such as cytotoxicity and target cell-induced cytokine produ...

An ideal vaccine for allergen-specific immunotherapy of type I allergies should display reduced mediator-releasing capacity, induce maturation of APC, and modify the disease-eliciting Th2-dominated allergen-specific response to a more physiological response. We have previously shown that rSbsC-Bet v 1, the recombinant fusion protein of a bacterial surface (S-layer) protein of Geobacillus stearo...