Abstract

The Fox/forkhead family encompasses an ever-growing number of helix-loop-helix transcription factors that participate in diverse biological systems. We describe here an immune role for Foxj1, a Fox family member originally characterized for its role in ciliated epithelial cells. In its absence, helper T (Th) cells are characterized by Th1-skewed hyperproliferation, associated with multi-system auto-inflammation. As such, Foxj1 plays a critical role in the maintenance of T cell quiescence and/or immune tolerance, but we know relatively little about its mechanism of action, as well as its contextual importance in T cell activation. We therefore propose in this application to delve further into the role of Foxj1 in T cell biology - in particular to examine more completely its role in Th proliferation and activation, to determine more fully its relevance to autoimmunity, and to elucidate the molecular pathway in which it operates. ? ? ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI061478-01
Application #
6815681
Study Section
Allergy and Immunology Study Section (ALY)
Program Officer
Esch, Thomas R
Project Start
2004-07-01
Project End
2009-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
1
Fiscal Year
2004
Total Cost
$344,250
Indirect Cost

  Institution

Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130

  Publications

Peng, Stanford L (2010) Forkhead transcription factors in chronic inflammation. Int J Biochem Cell Biol 42:482-5
Chen, Jing; Limon, Jose J; Blanc, Caroline et al. (2010) Foxo1 regulates marginal zone B-cell development. Eur J Immunol 40:1890-6
Gubbels Bupp, Melanie R; Edwards, Bonnie; Guo, Caiying et al. (2009) T cells require Foxo1 to populate the peripheral lymphoid organs. Eur J Immunol 39:2991-9
Bautista, Jhoanne L; Lio, Chan-Wang J; Lathrop, Stephanie K et al. (2009) Intraclonal competition limits the fate determination of regulatory T cells in the thymus. Nat Immunol 10:610-7
Lio, Chan-Wang Joaquim; Hsieh, Chyi-Song (2008) A two-step process for thymic regulatory T cell development. Immunity 28:100-11
Peng, S L (2006) Fas (CD95)-related apoptosis and rheumatoid arthritis. Rheumatology (Oxford) 45:26-30
Lin, Ling; Peng, Stanford L (2006) Coordination of NF-kappaB and NFAT antagonism by the forkhead transcription factor Foxd1. J Immunol 176:4793-803
Peng, S L (2005) Interplay between the NF-kappaB and forkhead transcription factors. Cell Death Differ 12:699-701
Peng, Stanford L (2005) Target identification and validation in systemic autoimmunity. Immunol Res 32:201-9
Lin, Ling; Brody, Steven L; Peng, Stanford L (2005) Restraint of B cell activation by Foxj1-mediated antagonism of NF-kappa B and IL-6. J Immunol 175:951-8

Showing the most recent 10 out of 14 publications