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 is RORC gene?
The RORC gene is a member of the nuclear receptor gene superfamily, which encode transcriptional regulators that play critical roles during homeostasis and specific stages of development (summary by Hirose et al., 1994).
What is Rorc immunology?
RAR-related orphan receptor gamma (RORγ) is a protein that in humans is encoded by the RORC (RAR-related orphan receptor C) gene. RORγ is member of the nuclear receptor family of transcription factors. It is mainly expressed in immune cells (Th17 cells) and it also regulates circadian rhythms.
Which transcription factor is characteristic of Th17 cells?
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 do Treg cells do?
Regulatory T cells (Tregs) are a specialized subpopulation of T cells that act to suppress immune response, thereby maintaining homeostasis and self-tolerance. It has been shown that Tregs are able to inhibit T cell proliferation and cytokine production and play a critical role in preventing autoimmunity.
What does ROR gamma t do?
Retinoid-related orphan receptor gamma t (RORgamma t) is a member of the nuclear receptor family that is specifically expressed in T cell compartments. RORgamma t regulates the development of T cells in the thymus and the differentiation of effector T cells in the periphery.
What is Th17 differentiation?
During Th17 differentiation, a complex interaction between strong antigenic signals and PAMP-dependent pathogenic stimuli induce CD40L expression, which increases IL-6 production from DCs for facilitating Th17 differentiation (41).
What cytokines activate Th17 cells?
IL-23 and IL-6, two cytokines that play a role in Th17 differentiation, also upregulate IL-22 production by Th17 cells (42, 44). IL-17 has been found to induce IL-6 production by human keratinocytes and thus may initiate a positive feedback loop resulting in amplification of both IL-17 and IL-22 responses in skin (67).
Do Th17 cells produce TNF?
These differentiated CD4+ T cells migrate to the dermis, where, by interacting with the innate immune system cells, they produce their typical inflammatory cytokines13. Th17 cells produce IL-17, IL-6, TNF-α, IL-21, and IL-2214; Th1 cells produce TNF-α and IFN-γ15; and Th22 cells produce IL-22 and TNF-α16.
What is the role of Treg cells?
How are RORα and RORγt expressed in Th17 cells?
Global gene expression profile was conducted in all the T cell samples from siRNA and compound studies by RNA-Seq. RORγt and RORα gene signatures were identified through differential gene expression analysis as described in the following sections. RORγt and RORα4 isoforms expressed in human Th17 cells
The Th17 Pathway: A New CD4 Effector T Cell Subset with Specialized Functions in Host Protection and New Implications for Chronic Inflammatory Diseases
What is the role of IL-6 and TGFβ in the Th17 pathway?
For the Th17 pathway, IL-6, TGFβ and IL-1β are critical early factors in specifying Th17 cell development through induction of the transcription factor, RORγt, encoded by the RORCgene. The inducible component of the IL-23 receptor complex, IL-23R, is upregulated downstream of RORγt expression and confers IL-23 responsiveness on maturing Th17 cells.
How to measure expression of Th17 genes in human TH17 cells?
Quantitative RT-PCR of RORα and RORγt signature genes Expression of RORα, RORγt and IL-17A genes in siRNA or compound treated human Th17 cells was measured by quantitative RT-PCR using the TaqMan RNA-to-Ct 1 step kit (Applied Biosystems) following the manufacturer’s instructions.