ROR gamma
RORγT Antibodies for Flow Cytometry and Western Blot Th17 Lineage
IL-17-producing CD4+ T cells (Th-17 cells) have been identified as a unique subset of Th cells that develops along a pathway that is distinct from the Th1- and Th2-cell differentiation pathways. One proposed mechanism is IL-23-dependent, but independent of STAT-1, T-bet, STAT4, and STAT6. The hallmark effector molecules of Th1 and Th2 cells, e.g., IFN-γ and IL-4, have each been found to negatively regulate the generation of these Th-17 cells. By a second proposed mechanism, de novo differentiation of Th-17 cells in the absence of IL-23 has been demonstrated by treatment of naïve CD4 cells with TGF-β1 and IL-6, an effect heightened by IL-1β and TNF-α; IL-23, though absent during the Th-17 differentiation, was still required for survival and expansion of the Th-17 cells. In EAE experiments, adoptive transfer of IL-23-polarized IL-17 effector cells is required for disease progression. Moreover, inhibition of the (negative-regulatory) IFN-γ signal has been found to lead to enhanced development of pathogenic Th-17 effector cells and autoimmune disease exacerbation.
IL-17 Biology
Interleukin-17 (IL-17) is a CD4+ T cell-derived cytokine that promotes inflammatory responses and is correlated with rheumatoid arthritis, asthma, multiple sclerosis, psoriasis, and transplant rejection. The cDNA encoding human IL-17 was isolated from a library of CD4+ T cells; the encoded protein exhibits 72 percent amino acid identity with HVS13 , an open reading frame from a T lymphotropic Herpesvirus saimiri, and 63 percent with mouse CTLA-8. Human IL-17 exists as glycosylated 20-30 kD homodimers. High levels of IL-17 homodimer are produced by activated peripheral blood CD4+ T-cells. IL-17 enhances expression of the intracellular adhesion molecule-1 (ICAM-1) in human fibroblasts. Human IL-17 also stimulates epithelial, endothelial, or fibroblastic cells to secrete IL-6, IL-8, G-CSF, and PGE2. In the presence of human IL-17, fibroblasts can sustain the proliferation of CD34+ hematopoietic progenitors and induce maturation into neutrophils. Mouse, rat, and human IL-17 can induce IL-6 secretion in mouse stromal cells, indicating that all homologs can recognize the mouse IL-17 receptor.
