Loss of Mef2D function enhances TLR induced IL-10 production in macrophages

Michael J. Pattison, Rangeetha Jayaprakash Naik, Kathleen M. S. E. Reyskens, J. Simon C. Arthur (Lead / Corresponding author)

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Abstract

Mef2 transcription factors comprise a family of 4 different isoforms that regulate a number of processes including neuronal and muscle development. While roles for Mef2C and Mef2D have been described in B cell development their role in immunity has not been extensively studied. In innate immune cells such as macrophages, TLRs drive the production of both proand anti-inflammatory cytokines. IL-10 is an important anti-inflammatory cytokine produced by macrophages and it establishes an autocrine feedback loop to inhibit pro-inflammatory cytokine production. We show here that macrophages from Mef2D knockout mice have elevated levels of IL-10 mRNA induction compared to wild type cells following LPS stimulation. The secretion of IL-10 was also higher from Mef2D knockout macrophages and this correlated to a reduction in the secretion of TNF, IL-6 and IL-12p40. The use of an IL-10 neutralising antibody showed that this reduction in pro-inflammatory cytokine production in the Mef2D knockouts was IL-10 dependent. As the IL-10 promoter has previously been reported to contain a potential binding site for Mef2D, it is possible that the binding of other Mef2 isoforms in the absence of Mef2D may result in a higher activation of the IL-10 gene. Further studies with compound Mef2 isoforms would be required to address this. We also show that Mef2D is highly expressed in the thymus, but that loss of Mef2D does not affect thymic T cell development or the production of IFNg from CD8 T cells.
Original languageEnglish
Article numberBSR20201859
Pages (from-to)1-15
Number of pages15
JournalBioscience Reports
Volume40
Issue number8
Early online date29 Jul 2020
DOIs
Publication statusPublished - 21 Aug 2020

Keywords

  • mef2D
  • macrophages
  • toll-like receptors
  • intracellular signaling

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