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Genetic and pharmacological inhibition of the nuclear receptor RORα regulates TH17 driven inflammatory disorders by Ran Wang; Sean Campbell; Mohammed Amir; Sarah A. Mosure; Molly A. Bassette; Amber Eliason; Mark S. Sundrud; Theodore M. Kamenecka; Laura A. Solt is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.
What is Genetic and pharmacological inhibition of the nuclear receptor RORα regulates TH17 driven inflammatory disorders about?
## Abstract Full development of IL-17 producing CD4^+^ T helper cells (T~H~17 cells) requires the transcriptional activity of both orphan nuclear receptors RORα and RORγt. However, RORα is considered functionally redundant to RORγt; therefore, the function and therapeutic value of RORα in T~H~17 cells is unclear. Here, using mouse models of autoimmune and chronic inflammation, we show that expression of RORα is required for T~H~17 cell pathogenicity. T-cell-specific deletion of RORα reduces the development of experimental autoimmune encephalomyelitis (EAE) and colitis. Reduced inflammation is associated with decreased T~H~17 cell development, lower expression of tissue-homing chemokine receptors and integrins, and increased frequencies of Foxp3^+^ T regulatory cells. Importantly, inhibition of RORα with a selective small molecule antagonist mostly phenocopies our genetic data, showing potent suppression of the in vivo development of both chronic/progressive and relapsing/remitting EAE, but with no effect on overall thymic cellularity. Furthermore, use of the RORα antagonist effectively inhibits human T~H~17 cell differentiation and memory cytokine secretion. Together, these data su
Who reads Genetic and pharmacological inhibition of the nuclear receptor RORα regulates TH17 driven inflammatory disorders?
It is typically read by researchers, students, and practitioners in Biochemistry, Genetics and Molecular Biology.
- Author
- Ran Wang; Sean Campbell; Mohammed Amir; Sarah A. Mosure; Molly A. Bassette; Amber Eliason; Mark S. Sundrud; Theodore M. Kamenecka; Laura A. Solt
- Publisher
- Springer Science and Business Media LLC
- Published
- 2021
- Language
- EN
- Field
- Biochemistry, Genetics and Molecular Biology (Life Sciences)