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NFIL3/E4BP4 controls type 2 T helper cell cytokine expression
Masaki Kashiwada1, Suzanne L Cassel, John D Colgan
1Department of Internal Medicine, University of Iowa, Iowa City, IA, USA.
The EMBO Journal
|April 19, 2011
Summary
The transcription factor NFIL3 regulates T helper 2 (T(H)2) cell function. NFIL3 controls allergic responses by modulating key cytokine production, impacting interleukin-13 and interleukin-5 levels.
Area of Science:
- Immunology
- Molecular Biology
- Transcription Factors
Background:
- Type 2 T helper (T(H)2) cells are crucial for allergic reactions.
- The precise molecular mechanisms governing T(H)2 cell effector functions remain incompletely understood.
Purpose of the Study:
- To investigate the role of the transcription factor NFIL3/E4BP4 in regulating T(H)2 cell cytokine production and effector functions.
- To elucidate the molecular mechanisms by which NFIL3 influences T(H)2 cell activity.
Main Methods:
- Analysis of NFIL3 expression in T(H)2 versus T(H)1 cells.
- Assessment of cytokine production (IL-13, IL-5, IL-4) in Nfil3 knockout (Nfil3(-/-)) T(H)2 cells and wild-type cells with NFIL3 expression.
- Chromatin immunoprecipitation assays to determine direct binding of NFIL3 to the Il13 gene.
- Evaluation of T(H)2 cytokine profiles in antigen-stimulated splenocytes from immunized Nfil3(-/-) mice.
Main Results:
- NFIL3 is highly expressed in T(H)2 cells compared to T(H)1 cells.
- Deletion of NFIL3 in T(H)2 cells led to significantly increased production of IL-13 and IL-5, and decreased IL-4 production.
- NFIL3 was found to directly bind and negatively regulate the Il13 gene.
- These effects on cytokine production were confirmed in antigen-stimulated splenocytes from Nfil3(-/-) mice and demonstrated to be T-cell intrinsic.
Conclusions:
- NFIL3 acts as a critical regulator of T(H)2 cell-mediated immune responses.
- NFIL3 controls the production of key T(H)2 cytokines, including IL-13 and IL-5, thereby modulating allergic inflammation.
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