The first transcription factor discovered, designated as the “lineage defining transcription factor of Th17 cells,” is RORγt, which is essential and sufficient to induce Th17 lineage fate in both human and mouse cells (5, 17, 25).
What are the transcription factor for differentiation of Th1 and Th17?
Like the suppressive function of FoxP3 on IL-17 expression, the Th1-specific transcription factor T-bet suppresses RORγt-mediated Th17 cell differentiation. Several functional studies indicate that T-bet suppresses RORγt expression and Th17 cell differentiation and further attenuates autoimmune responses.
What is the Th17 pathway?
The T helper 17 (Th17) cell pathway has been linked by genome-wide association studies to multiple autoimmune diseases. Identification of the genetic causes of primary immunodeficiency diseases revealed that Th17 cells are also critical in host immunity to mucocutaneous candida infections and Staphylococcus aureus.
What stimulates Th17 differentiation?
Lipopolysaccharide directly stimulates Th17 differentiation in vitro modulating phosphorylation of RelB and NF-κB1.
What transcription factor causes expression of Th1 phenotype?
T-bet is a Th1-specific transcription factor that plays a central role in Th1 development. T-bet transactivates the IFNγ gene, induces IFNγ production in retrovirally transduced primary T cells, and redirects polarized Th2 cells into the Th1 pathway.
Is Th17 inflammatory?
Trafficking of Th17 cells Inflammation and pathogenesis induced by Th17 cells is a result of the pro-inflammatory cytokines these cells produce, but another important and often overlooked factor is the chemokines and chemokine receptors that mediate trafficking of activated T cells into diseased tissue.
What is the function of Th17?
CD4 T cells play a key role in the functioning of a healthy immune system. They assist B cells to make antibodies, activate the microbe killing capacity of macrophages and recruit other immune cells to infected or inflamed areas of the body.
What stimulates Th17 cells?
Treg17 (Regulatory Th17) cells are generated from CD4+ T cells. Transforming growth factor beta (TGF-β), interleukin 6 (IL-6), interleukin 21 (IL-21) and interleukin 23 (IL-23) contribute to Th17 formation in mice and humans.
What is Th17 inflammation?
Inflammation and pathogenesis induced by Th17 cells is a result of the pro-inflammatory cytokines these cells produce, but another important and often overlooked factor is the chemokines and chemokine receptors that mediate trafficking of activated T cells into diseased tissue.
How are Th17 cells different from Th1 cells?
Th17 cells were the first subset identified as distinct from the original Th1/Th2 paradigm that had persisted for decades and were initially characterized based on their expression of IL-17A homodimers in response to IL-23 [ 1,3 ].
How does Ahr affect the differentiation of Th17 cells?
AHR is a nuclear factor shared with T regulatory cells but expressed at higher levels in Th17 cells, and while its deficiency does not impact Th17 differentiation, the production of effector cytokines, particularly IL-22, is significantly diminished [ 10 ].
Why are Th17 cells important to mucosal immunity?
While Th17 cells are critical for maintenance of mucosal immunity, their dysregulation has been implicated in the pathogenesis of autoimmune inflammation. It was their role in driving this inflammation that first suggested the presence of a third subset of CD4 + T helper cells distinct from the classical Th1/Th2 model.
What is the function of Th17 cytokines in the body?
Th17 effector function. Th17 cytokines exert a broad range of inflammatory and tissue-protective effects, particularly in mucosal immunity [ 26 ].