Preparing your results

Our searching services are busy right now. Your search will reload in five seconds.

X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Regulation of NF-kappaB, Th activation, and autoinflammation by the forkhead transcription factor Foxo3a.

Immunity | Aug 13, 2004

http://www.ncbi.nlm.nih.gov/pubmed/15308101

Forkhead (Fox) transcription factors play key roles in immunoregulation. Members of the Foxo subfamily have been implicated in the regulation of the cell cycle and/or apoptosis, but their specific immunological contexts remain largely undefined. We demonstrate here that Foxo3a, the predominant Foxo member expressed in peripheral lymphoid organs, plays a critical role in lymphoid homeostasis. Foxo3a deficiency leads to spontaneous lymphoproliferation, associated with inflammation of several organs, in the absence of overt apoptotic defects. These findings correlated with the presence of hyperactivated helper T cells, which proliferated more vigorously and produced more Th1 and Th2 cytokines than their wild-type counterparts. Foxo3a inhibits NF-kappaB activation, whose overactivity was responsible for T cell hyperactivity in Foxo3a-deficient mice. Thus, Foxo3a regulates helper T cell activation and tolerance by inhibiting NF-kappaB activity, reinforcing a generalized role for the forkhead proteins in the maintenance of T cell tolerance through the inhibition of inflammatory transcriptional activities.

Pubmed ID: 15308101 RIS Download

Mesh terms: Animals | Apoptosis | Autoimmunity | Cell Division | Forkhead Transcription Factors | Hypersensitivity | Inflammation | Lymphocyte Activation | Lymphoproliferative Disorders | Mice | NF-kappa B | T-Lymphocytes, Helper-Inducer | Transcription Factors

Research resources used in this publication

None found

Research tools detected in this publication

None found

Data used in this publication

None found

Associated grants

  • Agency: NIAID NIH HHS, Id: AI01803
  • Agency: NIAID NIH HHS, Id: AI057471I
  • Agency: NIAID NIH HHS, Id: AI061478
  • Agency: NIDDK NIH HHS, Id: DK52574

Mouse Genome Informatics (Data, Gene Annotation)

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.