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Related Experiment Video

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Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes

Isolation and Th17 Differentiation of Naïve CD4 T Lymphocytes

Published on: September 26, 2013

c-Maf regulates IL-10 expression during Th17 polarization.

Jiangnan Xu¹, Yu Yang, Guixing Qiu

¹Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.

Journal of Immunology (Baltimore, Md. : 1950)

|May 6, 2009

Summary

The transcription factor c-Maf regulates Interleukin-10 (IL-10) production in T helper 17 (Th17) cells, crucial for controlling inflammation. This finding reveals a new mechanism for managing autoimmune and inflammatory responses.

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Mouse Naïve CD4+ T Cell Isolation and In vitro Differentiation into T Cell Subsets

Mouse Naïve CD4⁺ T Cell Isolation and In vitro Differentiation into T Cell Subsets

Published on: April 16, 2015

Area of Science:

Immunology
Molecular Biology
Cellular Biology

Background:

Interleukin-10 (IL-10) production by T helper 17 (Th17) cells is vital for suppressing autoimmunity and inflammation.
Understanding the molecular mechanisms regulating Th17 cell differentiation and function is crucial for developing targeted therapies.

Purpose of the Study:

To identify novel transcription factors involved in IL-10 production by Th17 cells.
To elucidate the regulatory pathways controlling c-Maf and IL-10 expression in Th17 cells.
To investigate the role of c-Maf in T effector cell development and its potential impact on Th17 immunity.

Main Methods:

Gene array analysis of Stat6 and T-bet double-deficient Th17 cells.
Stimulation of Th17 cell polarization using cytokines like IL-6, TGF-beta, and IL-27.
Retroviral transduction to overexpress c-Maf in T cells.
Analysis of IL-10 promoter activity and transcription factor binding (Maf recognition element - MARE).

Main Results:

The Th2 transcription factor c-Maf was synergistically upregulated by IL-6 plus TGF-beta in Th17 cells and associated with IL-10 production.
Both c-Maf and IL-10 induction during Th17 polarization were dependent on Stat3, independent of Stat6 or Stat1.
TGF-beta synergized with IL-27 to induce c-Maf and Stat1-independent IL-10 expression.
Overexpression of c-Maf induced IL-10 expression in CD4 and CD8 T cells, directly transactivating the IL-10 gene via a MARE motif.

Conclusions:

c-Maf plays a novel role in regulating T effector cell development, specifically in promoting IL-10 production by Th17 cells.
TGF-beta may antagonize Th17 immunity by inducing IL-10 production through c-Maf.
These findings offer new insights into the regulation of immune responses and potential therapeutic targets for inflammatory diseases.