Publication Date:
2004-02-14
Description:
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-kappaB transcription activity in vitro, and Foxj1-deficient T cells possessed increased NF-kappaB activity in vivo, correlating with the ability of Foxj1 to regulate IkappaB proteins, particularly IkappaBbeta. 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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Lin, Ling -- Spoor, Melanie S -- Gerth, Andrea J -- Brody, Steven L -- Peng, Stanford L -- AI01803/AI/NIAID NIH HHS/ -- AI057471/AI/NIAID NIH HHS/ -- DK52574/DK/NIDDK NIH HHS/ -- HL56244/HL/NHLBI NIH HHS/ -- HL63988/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2004 Feb 13;303(5660):1017-20.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/14963332" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antigen-Presenting Cells/immunology
;
Autoimmunity
;
Cell Division
;
Cell Line
;
Cell Line, Tumor
;
Cell Nucleus/metabolism
;
Chimera
;
Cytoplasm/metabolism
;
DNA-Binding Proteins/genetics/*metabolism
;
Forkhead Transcription Factors
;
Gene Targeting
;
Humans
;
I-kappa B Proteins/genetics/metabolism
;
*Inflammation
;
Interferon-gamma/biosynthesis
;
Interleukin-2/immunology
;
Interleukins/biosynthesis
;
*Lymphocyte Activation
;
Mice
;
Mice, Inbred C57BL
;
NF-kappa B/antagonists & inhibitors/*metabolism
;
NFATC Transcription Factors
;
*Nuclear Proteins
;
Th1 Cells/*immunology
;
Th2 Cells/immunology
;
Transcription Factors/genetics/*metabolism
;
Transcriptional Activation
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink