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Review
. 2010 Jul;47(1-3):185-206.
doi: 10.1007/s12026-009-8150-5.

Cell type-specific regulation of IL-10 expression in inflammation and disease

Christian M Hedrich  1 , Jay H Bream
Affiliations
Review

Cell type-specific regulation of IL-10 expression in inflammation and disease

Christian M Hedrich et al. Immunol Res. 2010 Jul.

Abstract

IL-10 plays an essential part in controlling inflammation and instructing adaptive immune responses. Consequently, dysregulation of IL-10 is linked with susceptibility to numerous infectious and autoimmune diseases in mouse models and in humans. It has become increasingly clear that appropriate temporal/spatial expression of IL-10 may be the key to how IL-10 contributes to the delicate balance between inflammation and immunoregulation. The mechanisms that govern the cell type- and receptor-specific induction of IL-10, however, remain unclear. This is due largely to the wide distribution of cellular sources that express IL-10 under diverse stimulation conditions and in a variety of tissue compartments. Further complicating the issue is the fact that human IL-10 expression patterns appear to be under genetic influence resulting in differential expression and disease susceptibility. In this review, we discuss the cellular sources of IL-10, their link to disease phenotypes and the molecular mechanisms implicated in IL-10 regulation.

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Figures

Fig. 1
Fig. 1
Known regulatory regions within and flanking the IL10 gene. In the top panel, the physical organization of the IL10 cluster is displayed, including intergenic regions and distances between all genes in the cluster. The lower panel displays regions of epigenetic remodelling that have been investigated by various groups and in different cellular subsets. The tables beneath the figure explain the used symbols and give an overview on the cellular subsets and specific epigenetic modifications in each investigated region
Fig. 2
Fig. 2
Intergenic transcription around the mouse and human IL10 genes in BMM of hIL10BAC mice. Alignment of the human and mouse IL10 genes and surrounding sequences using human as the base genome for comparison (VISTA Genome Browser—http://pipeline.lbl.gov/cgi-bin/gateway2). The height of the peaks indicates the degree of sequence conservation. Noncoding sequences with a conservation degree of 70% or more over a length of 100 base pairs or more are shaded gray and indicated by black boxes and CNS numbers. Exons are shaded black and indicated by numbered black bars under the gene. The regions flanking the indicated CNS regions were analyzed for mouse and human transcripts and are indicated by boxes. DNA contamination was ruled out by including DNase treatment controls for each sample. The results are shown in boxes with thinner lines. Upper boxes indicate human transcripts, while lower boxes indicate mouse transcripts. −/+ represents no transcripts in non-stimulated (NS) cells but inducible transcripts after stimulation (LPS + IL-4). (+)/+ represents weak transcription in NS cells with inducible transcription after stimulation. −/− represents for no transcripts in NS cells or after stimulation. CNS3 here was reported as CNS-9 previously by Jones and Flavell and may act as enhancer element in Th1 and Th2 cells [169]. CNS4, which could be an origin of intergenic transcripts in human IL10 in macrophages, map to the previously reported CNS-20B that was shown to have basic promoter function in (transfected) D10 cells. CNS5 here maps to CNS-20A [169]
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