| Autor: |
Harbour SN; Department of Pathology., Maynard CL; Department of Pathology., Zindl CL; Department of Pathology., Schoeb TR; Department of Genetics, University of Alabama at Birmingham, Birmingham, AL 35294., Weaver CT; Department of Pathology cweaver@uab.edu. |
| Jazyk: |
angličtina |
| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2015 Jun 02; Vol. 112 (22), pp. 7061-6. Date of Electronic Publication: 2015 May 18. |
| DOI: |
10.1073/pnas.1415675112 |
| Abstrakt: |
Th17 cells reactive to the enteric microbiota are central to the pathogenesis of certain types of inflammatory bowel disease. However, Th17 cells display substantial developmental plasticity, such that some progeny of Th17 cell precursors retain a predominantly IL-17A(+) phenotype, whereas others extinguish IL-17 expression and acquire expression of IFN-γ, giving rise to "Th1-like" cells. It remains unclear what role these subsets play in inflammatory bowel disease. Using a Th17 transfer model of colitis, we found that IFN-γ-deficient Th17 cells retained an IL-17A(+) phenotype and were unable to induce colitis in recipients. Development of disease required the transition of a subset of Th17 precursors to Th1-like cells and was contingent on the expression of both Stat4 and T-bet, but not the IL-12 or IFN-γ receptors. Moreover, Th17 cells could provide "help" for the development of pathogenic Th1 cells from naïve precursors. These results indicate that Th17 cells are potent mediators of colitis pathogenesis by dual mechanisms: by directly transitioning to Th1-like cells and by supporting the development of classic Th1 cells. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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