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The regulation of IL-10 production by immune cells

Key Points

  • Interleukin-10 (IL-10) is not a cell type-specific cytokine, but instead it is broadly expressed by many immune cells.

  • Several layers of regulation regulate IL-10 production, including changes in the chromatin structure, enhancement or silencing of IL10 transcription and post-transcriptional regulatory mechanisms.

  • Many of the molecular events leading to IL10 expression are similar and common to various IL-10-producing immune cells, but cell type-specific signals also exist.

  • Induction of IL-10 often occurs together with pro-inflammatory cytokines, although pathways that induce IL-10 may actually negatively regulate these pro-inflammatory cytokines.

  • Understanding the specific molecular events that regulate the expression of IL-10 will be important for the design of new strategies of immune intervention.

Abstract

Interleukin-10 (IL-10), a cytokine with anti-inflammatory properties, has a central role in infection by limiting the immune response to pathogens and thereby preventing damage to the host. Recently, an increasing interest in how IL10 expression is regulated in different immune cells has revealed some of the molecular mechanisms involved at the levels of signal transduction, epigenetics, transcription factor binding and gene activation. Understanding the specific molecular events that regulate the production of IL-10 will help to answer the remaining questions that are important for the design of new strategies of immune intervention.

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Figure 1: Interleukin-10 expression in the immune system.
Figure 2: Signals that induce interleukin-10 expression by cells of the innate immune response.
Figure 3: Molecular regulation of interleukin-10 expression: the interleukin-10 locus and promoter.
Figure 4: Transcription factors that control interleukin-10 expression by CD4+ T cells and antigen-presenting cells.

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Acknowledgements

We thank L. Gabrysova for critical reading of and commenting on this review and A. Howes for careful proof reading.

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Glossary

Chromatin

Composed of nucleosomes, this is the basic repeating unit of eukaryotic genomes. Nucleosomes consist of 146 base pairs of DNA wound around an octamer of histone proteins.

Plasmacytoid DC

A DC that lacks myeloid markers such as CD11c and CD33 but expresses high levels of HLA-DR and CD123. These cells produce high levels of type I interferons in response to viral infection.

Notch

A signalling system comprising highly conserved transmembrane receptors that regulate cell fate choice in the development of many cell lineages. Therefore, they are crucial in the regulation of embryonic differentiation and development.

DNaseI hypersensitive sites

Sites of nuclease sensitivity in the nuclei on exposure of cells to limiting concentrations of DNaseI. The digested regions of DNA correspond to sites of open DNA, which might be factor-binding sites or areas of altered nucleosome conformation.

Chromatin remodelling

Alterations that are induced in chromatin by enzymes that modify the extent of acetylation, methylation or other covalent modifications of histones.

Acetylation

A post-translational modification of chromatin components, particularly histones. It correlates with actively transcribed chromatin.

T follicular helper cell

(TFH cell). A CD4+ T cell that provides help to B cells in follicles and germinal centres. The TFH cell signature includes the expression of CXCR5, ICOS, CD40 ligand and IL-21, factors that mediate TFH cell homing to follicles and B cell help.

MicroRNAs

Single-stranded RNA molecules of approximately 21–23 nucleotides in length that regulate the expression of other genes.

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Saraiva, M., O'Garra, A. The regulation of IL-10 production by immune cells. Nat Rev Immunol 10, 170–181 (2010). https://doi.org/10.1038/nri2711

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