| Autor: |
Afkarian M; Department of Pathology and Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, Box 8118, 660 S. Euclid Ave., St. Louis, MO 63110, USA., Sedy JR, Yang J, Jacobson NG, Cereb N, Yang SY, Murphy TL, Murphy KM |
| Jazyk: |
angličtina |
| Zdroj: |
Nature immunology [Nat Immunol] 2002 Jun; Vol. 3 (6), pp. 549-57. Date of Electronic Publication: 2002 May 13. |
| DOI: |
10.1038/ni794 |
| Abstrakt: |
T helper type 1 (T(H)1) cell development involves interferon-gamma (IFN-gamma) signaling through signal transducer and activator of transcription 1 (STAT1) and interleukin-12 (IL-12) signaling through STAT4 activation. We examined here T-bet regulation and evaluated the actions of T-bet in STAT1- and STAT4-dependent T(H)1 development processes. We found that T-bet expression during T cell activation was strongly dependent on IFN-gamma signaling and STAT1 activation, but was independent of STAT4. Ectopic T-bet expression strongly increased IFN-gamma production in T(H)2 cells activated by PMA-ionomycin, but weakly increased IFN-gamma production in T(H)2 cells stimulated by IL-12 IL-18 or OVA peptide antigen-presenting cell stimulation. In contrast, IL-12 IL-18 induced IFN-gamma production remained STAT4-dependent despite ectopic T-bet expression. Ectopic T-bet expression selectively induced expression of IL-12Rbeta2, but not IL-18Ralpha, in wild-type and STAT1(-/-) T(H)2 cells, but did not extinguish expression of GATA-3 and T(H)2 cytokines. Finally, ectopic T-bet did not directly induce expression of endogenous T- bet independently of IFN-gamma or STAT1. Thus, T-bet is induced by IFN-gamma and STAT1 signaling during T cell activation. In addition, T-bet mediates STAT1-dependent processes of T(H)1 development, including the induction of IL-12Rbeta2. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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