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The Regulation of IL-10 Expression

  • Leona Gabryšová
  • Ashleigh Howes
  • Margarida Saraiva
  • Anne O’Garra
Part of the Current Topics in Microbiology and Immunology book series (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.

Keywords

Il10 Gene Il10 Promoter Il10 Gene Expression Il10 Gene Promoter Il10 Gene Regulation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

List of 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

Notes

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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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Leona Gabryšová
    • 1
  • Ashleigh Howes
    • 1
  • Margarida Saraiva
    • 3
    • 4
  • Anne O’Garra
    • 1
    • 2
  1. 1.Division of ImmunoregulationMRC National Institute for Medical ResearchLondonUK
  2. 2.Department of Respiratory MedicineImperial College Healthcare NHS TrustLondonUK
  3. 3.Microbiology and Infection Research Domain, Life and Health Sciences Research Institute (ICVS), School of Health SciencesUniversity of MinhoBragaPortugal
  4. 4.ICVS/3B’s-PT Government Associate LaboratoryBraga/GuimarãesPortugal

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