| | |  | | | | Record from Web of Science® | | | | | | |
| The orphan nuclear receptor ROR gamma t directs the differentiation program of proinflammatory IL-17(+) T helper cells |
|
|
| Author(s): Ivanov II (Ivanov, Ivaylo I.), McKenzie BS (McKenzie, Brent S.), Zhou L (Zhou, Liang), Tadokoro CE (Tadokoro, Carlos E.), Lepelley A (Lepelley, Alice), Lafaille JJ (Lafaille, Juan J.), Cua DJ (Cua, Daniel J.), Littman DR (Littman, Dan R.) |
| Source: CELL Volume: 126 Issue: 6 Pages: 1121-1133 Published: SEP 22 2006 |
| Times Cited: 586 References: 58 |
| Abstract: IL-17-producing T lymphocytes have been recently shown to comprise a distinct lineage of proinflammatory T helper cells, termed Th17 cells, that are major contributors to autoimmune disease. We show here that the orphan nuclear receptor ROR gamma t is the key transcription factor that orchestrates the differentiation of this effector cell lineage. ROR gamma t induces transcription of the genes encoding IL-17 and the related cytokine IL-17F in naive CD4(+) T helper cells and is required for their expression in response to IL-6 and TGF-beta, the cytokines known to induce IL-17. Th17 cells are constitutively present throughout the intestinal lamina propria, express ROR gamma t, and are absent in mice deficient for ROR gamma t or IL-6. Mice with ROR gamma t-deficient T cells have attenuated autoimmune disease and lack tissue-infiltrating Th17 cells. Together, these studies suggest that ROR gamma t is a key regulator of immune homeostasis and highlight its potential as a therapeutic target in inflammatory diseases. |
| Document Type: Article |
| Language: English |
| Reprint Address: Cua, DJ (reprint author), NYU, Sch Med, Skirball Inst Biomol Med, Mol Pathogenesis Program, 550 1St Ave, New York, NY 10016 USA |
Addresses:
1. NYU, Sch Med, Skirball Inst Biomol Med, Mol Pathogenesis Program, New York, NY 10016 USA
2. NYU, Sch Med, Howard Hughes Med Inst, Skirball Inst Biomol Med, New York, NY 10016 USA
3. Schering Plough BioPharm, DNAX Discovery Res, Palo Alto, CA 94304 USA |
| Publisher: CELL PRESS, 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA |
| Subject Category: Biochemistry & Molecular Biology; Cell Biology |
| IDS Number: 089RF |
| ISSN: 0092-8674 |
| DOI: 10.1016/j.cell.2006.07.035 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |