BET (bromodomain and extra-terminal) proteins regulate gene expression through their ability to bind to acetylated chromatin and subsequently activate RNA PolII-driven transcriptional elongation. Small molecule BET inhibitors prevent binding of BET proteins to acetylated histones and inhibit transcriptional activation of BET target genes. BET inhibitors attenuate cell growth and survival in sev...

T-bet is a transcription factor of the T-box family that regulates the expression of numerous immune system-associated genes. T-bet directs the acquisition of the Th1-associated genetic program in differentiating CD4(+) lymphocytes. It also influences the development of NK and NKT cells through its regulation of the IL-2/IL-15Rbeta-chain (CD122) and the trafficking of these lymphocytes through ...

Given the association with autoimmune disease, there is great interest in defining cellular factors that limit overactive or misdirected Th17-type inflammation. Using in vivo and in vitro models, we investigated the molecular mechanisms for cytokine-mediated inhibition of Th17 responses, focusing on the role of STAT1 and T-bet in this process. These studies demonstrate that, during systemic inf...

Counterregulating the disease-eliciting Th2-like immune response of allergen-specific Th lymphocytes by fostering an allergen-specific Th1-like response is a promising concept for future immunotherapy of type I allergy. The use of recombinant allergens combined with more functional adjuvants has been proposed. In this respect, we present a novel approach. The gene sequence encoding the major bi...

As a means of developing therapies that target the pathogenic T cells in multiple sclerosis (MS) without compromising the immune system or eliciting systemic side effects, we investigated the use of T-bet-specific antisense oligonucleotides and small interfering RNAs (siRNA) to silence T-bet expression in autoreactive encephalitogenic T cells and evaluated the biological consequences of this su...

T cells that produce both IL-17 and IFN-γ, and co-express ROR-γt and T-bet, are often found at sites of autoimmune inflammation. However, it is unknown whether this co-expression of T-bet with ROR-γt is a prerequisite for immunopathology. We show here that T-bet is not required for the development of Th17-driven experimental autoimmune encephalomyelitis (EAE). The disease was not impaired in T-...

In Northern America and Europe a great number of people are suffering from birch pollen allergy and pollen related food allergies. The trigger for these immunological reactions is the 17.5 kDa major birch pollen allergen Bet v 1, which belongs to the family of PR-10 (pathogenesis-related) proteins. In nature, Bet v 1 occurs as a mixture of various isoforms that possess different immunological p...

BACKGROUND Birch allergy (BA) is a common pollinosis caused by the allergens Bet v 1, Bet v 2, and Bet v 4. Oral allergy syndrome (OAS) is frequently associated with BA. A gradient of sensitization to birch allergen across Europe has been reported. Therefore, this study aimed to investigate the birch sensitization profile, including OAS, across Italy. METHODS We performed a retrospective stud...

In this issue of the Journal, Dorfman and colleagues1 describe the usefulness of T-bet as a marker for specific subtypes of B-cell lymphoma. T-bet originally was identified as a T-box family transcription factor that dominantly programs CD4 and CD8 T-cell development along Th1 and Tc1 pathways, respectively.2 It accomplished this impressive task in part through the coordinated transcriptional a...