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PMID: 21499227 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

NFIL3/E4BP4 controls type 2 T helper cell cytokine expression.

The EMBO journal ·Vol. 30 ·No. 10 ·2011-05-18 ·Pages 2071-82

Kashiwada M, Cassel SL, Colgan JD, Rothman PB

Abstract

Type 2 T helper (T(H)2) cells are critical for the development of allergic immune responses; however, the molecular mechanism controlling their effector function is still largely unclear. Here, we report that the transcription factor NFIL3/E4BP4 regulates cytokine production and effector function by T(H)2 cells. NFIL3 is highly expressed in T(H)2 cells but much less in T(H)1 cells. Production of interleukin (IL)-13 and IL-5 is significantly increased in Nfil3(-/-) T(H)2 cells and is decreased by expression of NFIL3 in wild-type T(H)2 cells. NFIL3 directly binds to and negatively regulates the Il13 gene. In contrast, IL-4 production is decreased in Nfil3(-/-) T(H)2 cells. Increased IL-13 and IL-5 together with decreased IL-4 production by antigen-stimulated splenocytes from the immunized Nfil3(-/-) mice was also observed. The ability of NFIL3 to alter T(H)2 cytokine production is a T-cell intrinsic effect. Taken together, these data indicate that NFIL3 is a key regulator of T(H)2 responses.

MeSH Terms
Animals Basic-Leucine Zipper Transcription Factors/metabolism Gene Expression Regulation Interleukin-13/biosynthesis Interleukin-4/biosynthesis Interleukin-5/biosynthesis Mice Mice, Inbred C57BL Mice, Knockout Th2 Cells/immunology,metabolism Transcription, Genetic
Chemicals
Basic-Leucine Zipper Transcription Factors Interleukin-13 Interleukin-5 Nfil3 protein, mouse Interleukin-4
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Kashiwada Masaki
Department of Internal Medicine, University of Iowa, Iowa City, IA, USA.
Cassel Suzanne L
Colgan John D
Rothman Paul B
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
1460-2075
DOI
10.1038/emboj.2011.111
Published
2011-05-18
Epub
2011-00-15
Pages
2071-82
Language
English
Region
England
NLM ID
8208664
PMCID
PMC3098483
Subset
IM
Grants
NIAID NIH HHS · R01 AI054821-10 · United States
NIAID NIH HHS · R01 AI054821 · United States
NIAID NIH HHS · R01 AI067489-05 · United States
NIAID NIH HHS · R01 AI067489 · United States
NIAID NIH HHS · R01 AI54821 · United States
External Links
PubMed source DOI: 10.1038/emboj.2011.111 PMC Full Text View journal details
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