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Science 303 (5660): 1017-1020

Copyright © 2004 by the American Association for the Advancement of Science

Modulation of Th1 Activation and Inflammation by the NF-{kappa}B Repressor Foxj1

Ling Lin,1 Melanie S. Spoor,2 Andrea J. Gerth,1 Steven L. Brody,2 Stanford L. Peng1,3*

Abstract: Forkhead transcription factors play key roles in the regulation of immune responses. Here, we identify a role for one member of this family, Foxj1, in the regulation of T cell activation and autoreactivity. Foxj1 deficiency resulted in multiorgan systemic inflammation, exaggerated Th1 cytokine production, and T cell proliferation in autologous mixed lymphocyte reactions. Foxj1 suppressed NF-{kappa}B transcription activity in vitro, and Foxj1-deficient T cells possessed increased NF-{kappa}B activity in vivo, correlating with the ability of Foxj1 to regulate I{kappa}B proteins, particularly I{kappa}Bß. Thus, Foxj1 likely modulates inflammatory reactions and prevents autoimmunity by antagonizing proinflammatory transcriptional activities. These results suggest a potentially general role for forkhead genes in the enforcement of lymphocyte quiescence.

1 Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
2 Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.
3 Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.

* To whom correspondence should be addressed. E-mail: speng{at}im.wustl.edu


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