Publication Date:
2009-07-07
Description:
Activator protein 1 (AP-1, also known as JUN) transcription factors are dimers of JUN, FOS, MAF and activating transcription factor (ATF) family proteins characterized by basic region and leucine zipper domains. Many AP-1 proteins contain defined transcriptional activation domains, but BATF and the closely related BATF3 (refs 2, 3) contain only a basic region and leucine zipper, and are considered to be inhibitors of AP-1 activity. Here we show that Batf is required for the differentiation of IL17-producing T helper (T(H)17) cells. T(H)17 cells comprise a CD4(+) T-cell subset that coordinates inflammatory responses in host defence but is pathogenic in autoimmunity. Batf(-/-) mice have normal T(H)1 and T(H)2 differentiation, but show a defect in T(H)17 differentiation, and are resistant to experimental autoimmune encephalomyelitis. Batf(-/-) T cells fail to induce known factors required for T(H)17 differentiation, such as RORgamma t (encoded by Rorc) and the cytokine IL21 (refs 14-17). Neither the addition of IL21 nor the overexpression of RORgamma t fully restores IL17 production in Batf(-/-) T cells. The Il17 promoter is BATF-responsive, and after T(H)17 differentiation, BATF binds conserved intergenic elements in the Il17a-Il17f locus and to the Il17, Il21 and Il22 (ref. 18) promoters. These results demonstrate that the AP-1 protein BATF has a critical role in T(H)17 differentiation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2716014/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2716014/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Schraml, Barbara U -- Hildner, Kai -- Ise, Wataru -- Lee, Wan-Ling -- Smith, Whitney A-E -- Solomon, Ben -- Sahota, Gurmukh -- Sim, Julia -- Mukasa, Ryuta -- Cemerski, Saso -- Hatton, Robin D -- Stormo, Gary D -- Weaver, Casey T -- Russell, John H -- Murphy, Theresa L -- Murphy, Kenneth M -- AI035783/AI/NIAID NIH HHS/ -- AR049293/AR/NIAMS NIH HHS/ -- GM07200/GM/NIGMS NIH HHS/ -- HG00249/HG/NHGRI NIH HHS/ -- R01 HG000249/HG/NHGRI NIH HHS/ -- R01 HG000249-20/HG/NHGRI NIH HHS/ -- T32 GM008802/GM/NIGMS NIH HHS/ -- T32 GM008802-08/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2009 Jul 16;460(7253):405-9. doi: 10.1038/nature08114. Epub 2009 Jul 5.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pathology and Immunology, Washington University School of Medicine, 660 South Euclid Avenue, Saint Louis, Missouri 63110, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19578362" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Basic-Leucine Zipper Transcription Factors/deficiency/genetics/*metabolism
;
*Cell Differentiation
;
Encephalomyelitis, Autoimmune, Experimental/genetics
;
Female
;
Gene Expression Regulation
;
Genetic Predisposition to Disease
;
Interleukin-17/biosynthesis/genetics/*metabolism
;
Interleukins/genetics/metabolism/pharmacology
;
Lymph Nodes/metabolism
;
Male
;
Mice
;
Nuclear Receptor Subfamily 1, Group F, Member 3
;
Promoter Regions, Genetic/genetics
;
Receptors, Retinoic Acid/genetics/metabolism
;
Receptors, Thyroid Hormone/genetics/metabolism
;
T-Lymphocytes, Helper-Inducer/*cytology/*metabolism
;
Transcription Factor AP-1/deficiency/genetics/*metabolism
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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