Forkhead and Autoimmunity

Science's STKE  17 Feb 2004:
Vol. 2004, Issue 220, pp. tw65-TW65
DOI: 10.1126/stke.2202004TW65

The forkhead family of transcription factors are involved in a variety of systems. The forkhead family member Foxj1 is thought to play a role in the immune system, but genetic deficiency of this factor proves lethal, making direct in vivo analysis difficult. To overcome this, Lin et al. devised a chimeric system in mice, in which effects of Foxj1 deficiency could be explored. In these chimeras, foxj1−/− T cells displayed an exaggerated inflammatory cytokine expression, which eventually generated systemic autoimmunity. Normal repression of cytokine production by Foxj1 resulted from inhibition of the transcriptional activator nuclear factor NF-κB, possibly via the up-regulation of the inhibitory NF-κB cofactor, IκB.

L. Lin, M. S. Spoor, A. J. Gerth, S. L. Brody, S. L. Peng, Modulation of TH1 activation and inflammation by the NF-κB repressor Foxj1. Science 303, 1017-1020 (2004). [Abstract] [Full Text]