Identification of a Selective RORγ Ligand That Suppresses T(H)17 Cells and Stimulates T Regulatory Cells.
Summary of "Identification of a Selective RORγ Ligand That Suppresses T(H)17 Cells and Stimulates T Regulatory Cells."
Nuclear receptors (NRs) are ligand-regulated transcription factors, many of which are validated targets for clinical purposes. The retinoic acid receptor-related orphan nuclear receptors alpha and gamma t (RORα and RORγt) are considered to be the master regulators of development of T(H)17 cells, a subset of T cells that have been implicated in the pathology of several autoimmune diseases, including multiple sclerosis (MS) and rheumatoid arthritis (RA). We report here the identification of a novel RORγ-specific synthetic ligand, SR1555, that not only inhibits T(H)17 cell development and function but also increases the frequency of T regulatory cells. Our data suggests synthetic RORγ ligands can be developed that target both suppression of T(H)17 and stimulation of T regulatory cells, offering key advantages in development of therapeutics targeting autoimmune diseases.
Affiliation
The Scripps Research Institute, Jupiter, Florida 33458, United States.
Journal Details
This article was published in the following journal.
Name: ACS chemical biology
ISSN: 1554-8937
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/22769242
- DOI: http://dx.doi.org/10.1021/cb3002649
Medical and Biotech [MESH] Definitions
T-lymphocytes, Regulatory
CD4-positive T cells that inhibit immunopathology or autoimmune disease in vivo. They inhibit the immune response by influencing the activity of other cell types. Regulatory T-cells include naturally occurring CD4+CD25+ cells, IL-10 secreting Tr1 cells, and Th3 cells.
Cd40 Ligand
A membrane glycoprotein and differentiation antigen expressed on the surface of T-cells that binds to CD40 ANTIGENS on B-LYMPHOCYTES and induces their proliferation. Mutation of the gene for CD40 ligand is a cause of HYPER-IGM IMMUNODEFICIENCY SYNDROME, TYPE 1.
4-1bb Ligand
A membrane bound member of the TNF superfamily that is expressed on activated B-LYMPHOCYTES; MACROPHAGES; and DENDRITIC CELLS. The ligand is specific for the 4-1BB RECEPTOR and may play a role in inducing the proliferation of activated peripheral blood T-LYMPHOCYTES.
Gamma-msh
An 11-amino acid peptide derived from the N-terminal fragment of pro-opiomelanocortin (POMC). Gamma-MSH stimulates adrenal steroidogenesis and has an regulatory role in the cardiovascular and the renal systems.
Tnf-related Apoptosis-inducing Ligand
A transmembrane-protein belonging to the TNF family of intercellular signaling proteins. It is a widely expressed ligand that activates APOPTOSIS by binding to TNF-RELATED APOPTOSIS-INDUCING LIGAND RECEPTORS. The membrane-bound form of the protein can be cleaved by specific CYSTEINE ENDOPEPTIDASES to form a soluble ligand form.
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