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The Regulation of IL-10 Expression

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Interleukin-10 in Health and Disease

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 380))

Abstract

Interleukin (IL)-10 is an important immunoregulatory cytokine and an understanding of how IL-10 expression is controlled is critical in the design of immune intervention strategies. IL-10 is produced by almost all cell types within the innate (including macrophages, monocytes, dendritic cells (DCs), mast cells, neutrophils, eosinophils and natural killer cells) and adaptive (including CD4+ T cells, CD8+ T cells and B cells) immune systems. The mechanisms of IL-10 regulation operate at several stages including chromatin remodelling at the Il10 locus, transcriptional regulation of Il10 expression and post-transcriptional regulation of Il10 mRNA. In addition, whereas some aspects of Il10 gene regulation are conserved between different immune cell types, several are cell type- or stimulus-specific. Here, we outline the complexity of IL-10 production by discussing what is known about its regulation in macrophages, monocytes, DCs and CD4+ T helper cells.

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Abbreviations

AHR:

Aryl hydrocarbon receptor

AP-1:

Activator protein 1

APC:

Antigen presenting cell

ARE:

AU rich element

ATF:

Activating transcription factor 1

AUF-1:

ARE/poly(U) binding degradation factor 1

BATF:

Basic leucine zipper transcription factor ATF-like transcription factor

BCL-6:

B-cell lymphoma 6

BLIMP-1:

PR domain zinc finger protein 1

BM:

Bone marrow

C/EBP:

CCAAT/enhancer binding protein

cAMP:

Cyclic adenosine monophosphate

CBP:

CREB-binding protein

CD40L:

CD40 ligand

ChIP-Seq:

Chromatin immunoprecipitation-sequencing

CNS:

Conserved non-coding sequences

CREB:

cAMP response element-binding protein

CRTC3:

CREB-regulated transcription coactivator 3

DC:

Dendritic cell

DLL:

Delta-like Notch ligands

DRE:

Distal regulatory element

DUSP1:

Dual specificity phosphatase-1

E4BP4:

E4 promoter-binding protein 4

ERK:

Extracellular signal-regulated kinase

E. coli :

Escherichia coli

ETS-1:

E26 transformation-specific 1

GATA3:

GATA binding protein 3

GM-CSF:

Granulocyte-monocyte colony stimulating factor

GSK3:

Glycogen synthase kinase 3

HAT:

Histone acetyl transferase

HDAC:

Histone deacetylase

HMT:

Histone methyl transferase

HSS:

DNaseI hypersensitive sites

ICOS:

Inducible T cell costimulator

IFN:

Interferon

IL:

Interleukin

IRF:

Interferon regulatory factor

JDP:

Jun dimerising protein

LPS:

Lipopolysaccharide

MAP kinase:

Mitogen-activated protein kinase

MARE:

C-MAF responsive element

mDC:

Myeloid dendritic cell

MHC:

Major histocompatibility complex

miRNA:

MicroRNA

MSK1/2:

Mitogen- and stress-activated protein kinases 1/2

mTOR:

Mammalian target of rapamycin

M. tuberculosis :

Mycobacterium tuberculosis

MyD88:

Myeloid differentiation factor 88

NF-κB:

Nuclear factor-κB

NFAT:

Nuclear factor of activated T cells

PBX1:

Pre-B cell leukaemia homeobox 1

pDC:

Plasmocytoid dendritic cell

PDCD4:

Programmed cell death 4

PGE2:

Prostaglandin E2

PI(3)K:

Phosphatidylinositol 3 kinase

PKA:

Protein kinase A

PKR:

Protein kinase R

PREP1:

PBX-regulating protein 1

PRR:

Pattern recognition receptor

RORγt:

RAR-related orphan receptor gamma t

SIK2:

Salt-inducible kinase 2

Sp1/3:

Specific protein 1/3

STAT:

Signal transducer and activator of transcription

SWI/SNF:

Switching-defective-sucrose non-fermenting

SYK:

Spleen tyrosine kinase

TBET:

T-box transcription factor

TCR:

T cell receptor

Tfh:

T follicular helper cell

TGF:

Transforming growth factor

Th:

T helper cell

TLR:

Toll-like receptor

TNF:

Tumour necrosis factor

TPL-2:

Tumour progression locus 2

TRIF:

TIR-domain-containing adapter-inducing interferon-β

TSS:

Transcription start site

TTP:

Tristetraprolin

UTR:

Untranslated region

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Acknowledgments

At NIMR, we thank B. Seddon, C. Sinclair and S. Ley for discussions, J. Brock from PhotoGraphics for the generation of figures and C. Whicher for critical reading of the manuscript. MS is a FCT Associate Investigator. AOG, LG, AH are funded by UK MRC (U117565642); AOG. is also funded by Imperial College, National Heart and Lung Institute; AOG & LG are also funded by ERC-2011-AdG, 294682-TB-PATH; MS is funded by Fundação para a Ciência e Tecnologia, Portugal and co-funded by Programa 73 Operacional Regional do Norte (ON.2 – O Novo Norte), Quadro de Referência Estratégico Nacional 74 (QREN), through the Fundo Europeu de Desenvolvimento Regional (FEDER).

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Authors and Affiliations

  1. Division of Immunoregulation, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London, NW7 1AA, UK

    Leona Gabryšová, Ashleigh Howes & Anne O’Garra

  2. Department of Respiratory Medicine, Imperial College Healthcare NHS Trust, St. Mary’s Hospital, London, W2 1NY, UK

    Anne O’Garra

  3. Microbiology and Infection Research Domain, Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal

    Margarida Saraiva

  4. ICVS/3B’s-PT Government Associate Laboratory, Campus Gualtar, 4710-057, Braga/Guimarães, Portugal

    Margarida Saraiva

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  1. Leona Gabryšová
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  2. Ashleigh Howes
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  3. Margarida Saraiva
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  4. Anne O’Garra
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Correspondence to Anne O’Garra .

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Editors and Affiliations

  1. Deutsches Rheuma-Forschungszentrum Berlin, Berlin, Germany

    Simon Fillatreau

  2. Div. of Immunoregulation, The MRC National Institute for Medical Research, London, United Kingdom

    Anne O'Garra

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Gabryšová, L., Howes, A., Saraiva, M., O’Garra, A. (2014). The Regulation of IL-10 Expression. In: Fillatreau, S., O'Garra, A. (eds) Interleukin-10 in Health and Disease. Current Topics in Microbiology and Immunology, vol 380. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-43492-5_8

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