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Foxd3 suppresses interleukin-10 expression in B cells.

Yu Zhang1,2, Zhiding Wang2,3, He Xiao2

  • 1College of Pharmacy, Henan University, Kaifeng, China.

Immunology
|December 21, 2016
PubMed
Summary

Foxd3 transcription factor suppresses Interleukin-10-positive regulatory B cell production by binding the IL-10 promoter. Targeting Foxd3 may offer new treatments for autoimmune diseases.

Keywords:
Foxd3interleukin-10lupus-prone miceregulatory B cells

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Area of Science:

  • Immunology
  • Molecular Biology
  • Transcription Factor Regulation

Background:

  • Regulatory B (Breg) cells secrete Interleukin-10 (IL-10) to control inflammation.
  • Key transcription factors governing Breg cell differentiation and IL-10 expression remain largely unknown.

Purpose of the Study:

  • To identify transcription factors regulating IL-10 expression in Breg cells.
  • To elucidate the mechanism by which Foxd3 influences Breg cell production.

Main Methods:

  • Bioinformatic prediction of transcription factor binding sites on the IL-10 promoter.
  • Chromatin immunoprecipitation PCR (ChIP-PCR) to confirm Foxd3 binding.
  • Reporter gene assays to assess IL-10 promoter activity.
  • Foxd3 knockout studies and analysis in lupus-prone mice.

Main Results:

  • Foxd3 was predicted and confirmed to bind directly to the IL-10 promoter.
  • Foxd3 was found to suppress IL-10 promoter activity.
  • Foxd3 knockout enhanced IL-10 expression and Breg cell production.
  • Foxd3 expression inversely correlated with IL-10-positive Breg cells in MRL/lpr mice.

Conclusions:

  • Foxd3 acts as a negative regulator of IL-10-positive Breg cell production by directly binding the IL-10 promoter.
  • Foxd3 presents a potential therapeutic target for modulating Breg cell function in autoimmune diseases.