REVIEW
Biological properties and regulation of IL-10 related cytokines and their contribution to autoimmune disease and tissue injury

https://doi.org/10.1016/j.clim.2012.02.005Get rights and content

Abstract

The IL-10 cytokine family has nine members, four of which are located in the IL10 cluster on chromosome 1q32. These cytokines are the immune regulatory cytokine IL-10 itself, and the IL-20 subfamily members IL-19, IL-20, and IL-24. IL-10 instructs innate and adaptive immune responses and limits pro-inflammatory responses in order to prevent tissue damage. The IL-20 subfamily members are involved in host defense mechanisms, particularly from epithelial cells and seem essential for tissue integrity. Dysregulation of IL-10 family cytokines results in inflammation and autoimmune disease. Here, we discuss cellular source, gene regulation, and receptor complexes of cytokines in the IL10 cluster and their contribution to autoimmune disease and tissue damage.

Highlights

ā–ŗ The IL10 cytokine cluster on chromosome 1 harbors IL10, IL19, IL20, and IL24. ā–ŗ The namesake cytokine IL-10 controls immune responses and prevents tissue damage. ā–ŗ The IL-20 subfamily members regulate innate immune responses to infections. ā–ŗ IL-20 subfamily cytokines induce wound healing and play a role in tissue integrity. ā–ŗ Dysregulation of IL-10 related cytokines and receptors contribute to autoimmunity.

Introduction

Pro- and anti-inflammatory cytokines are key mediators during immune responses. Cytokines mediate defense mechanisms to antigen contact between cells and tissues, thus determining the quality (inflammatory or anti-inflammatory) and nature (humoral, cellular, and/or cytotoxic) of immune responses (1).

The IL-10 family of cytokines consists of nine related molecules with ranging degrees of sequence homology. IL-10 family members can be sub-divided into three groups with different biological functions: 1) the immune-regulatory cytokine IL-10 itself; 2) the IL-20 subfamily: IL-19, IL-20, IL-22, IL-24, and IL-26 which play a role in host-defense mechanisms against bacteria and fungi; and 3) the type III interferons: IL-28A, IL-28B, and IL-29 which induce antiviral responses [2], [3]. For some of the aforementioned cytokines, convincing data is available which has revealed their biological function(s); some cytokines have dual effects with pro- and anti-inflammatory capacities; for other cytokines the biological function and their significance during immune responses remain to be determined.

Interestingly, the IL10, IL19, IL20, and IL24 genes are located within the 145Ā kb spanning IL-10 cytokine cluster on chromosome 1q32 (4). The genes, encoding for the two family members IL-22 and IL-26 are located within 30Ā kb of each other and less than 100Ā kb apart from the interferon-Ī³ (IFNG) gene on chromosome 12q15. The IL28A, IL28B and IL29 genes are located on chromosome 19q13 [1], [3].

In this review, we discuss (known) cellular sources, stimuli, and signaling pathways of those IL-10-related cytokines that are located within the IL10 cluster on chromosome 1q32 (Fig.Ā 1). Furthermore, we discuss their involvement in the pathophysiology of autoimmune diseases.

Section snippets

Biological function, cellular sources and receptors

The namesake cytokine IL-10 plays a central role during innate and adaptive immune responses (5). It was first documented to inhibit Th1 activation and cytokine production, thus named cytokine synthesis inhibitory factor (CSIF) (6). The IL10 gene is located on chromosome 1q32 and is in close physical relationship to the IL-10 cytokine family members IL19, IL20, and IL24 (Fig.Ā 1).

IL-10 is a ubiquitously expressed cytokine. Main sources in the immune system are T lymphocytes (mainly Th2 subsets),

Conclusions

In this review, we limit our discussion to IL-10-related cytokines that are located within the IL10 cluster on chromosome 1q32. A tight balance between IL-10 and the IL-20 subfamily members is essential for the protection of tissues and organs from inflammation and infections. Cytokines within the IL10 cluster seem to have four main functions: 1) the defining cytokine IL-10 controls innate and adaptive immune responses and prevents tissue damage; 2) IL-20 subfamily cytokines trigger and

Conflict of interest statement

The authors declare that there are no conflicts of interest.

Acknowledgments

This work was supported by MeDDrive 2010 (University Medical Center Carl Gustav Carus, University of Technology Dresden, Germany) to C.M.H. S.R.H. and A.R.-W. are supported by the German Research Foundation (Klinische Forschergruppe KFO 249, project TP2, HO 4510/1-1 and TP1,35 RO/471-11).

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