Interleukin 31, a cytokine produced by activated T cells, induces dermatitis in mice

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  • An Erratum to this article was published on 01 January 2005

Abstract

T cell–derived cytokines are important in the development of an effective immune response, but when dysregulated they can promote disease. Here we identify a four-helix bundle cytokine we have called interleukin 31 (IL-31), which is preferentially produced by T helper type 2 cells. IL-31 signals through a receptor composed of IL-31 receptor A and oncostatin M receptor. Expression of IL-31 receptor A and oncostatin M receptor mRNA was induced in activated monocytes, whereas epithelial cells expressed both mRNAs constitutively. Transgenic mice overexpressing IL-31 developed severe pruritis, alopecia and skin lesions. Furthermore, IL-31 receptor expression was increased in diseased tissues derived from an animal model of airway hypersensitivity. These data indicate that IL-31 may be involved in promoting the dermatitis and epithelial responses that characterize allergic and non-allergic diseases.

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Figure 1: IL-31 signals through IL-31RA and OSMR.
Figure 2: Expression analysis of IL-31 by real-time PCR.
Figure 3: Expression analysis of IL-31RA and OSMR mRNA in human and mouse samples by real-time PCR.
Figure 4: IL-31-transgenic lesional skin is characterized by many hallmarks of atopic dermatitis.
Figure 5: IL-31-transgenic mice have enlarged peripheral lymph nodes containing an inverted ratio of T lymphocytes to B lymphocytes and an increased number of activated CD4+ and CD8+ T cells.
Figure 6: Intradermal injection of IL-31 causes cell infiltration and acanthosis.
Figure 7: IL-31RA-deficient mice do not develop pruritis or alopecia when given mouse IL-31 by osmotic pump.
Figure 8: IL-31RA mRNA is upregulated in lung and bronchoalveolar lavage cells after allergen sensitization.

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Acknowledgements

We thank K. Kim, K. Bontadelli and D. Cutler for help with the generation and analysis of the IL-31-transgenic mice; K. Bannink for the IL-31 in vivo treatment studies; T. Whitmore for insights regarding the gene array analysis and genetic linkage analysis; and M. Bernard for assistance in preparing the manuscript.

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Correspondence to Jane A Gross.

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Competing interests

The authors of this manuscript are employed or previously employed by ZymoGenetics Inc. and may or may not benefit financially from the publication of this paper.

Supplementary information

Supplementary Table 1

STAT activation by IL-31 in human cells (PDF 4 kb)

Supplementary Table 2

Induction of chemokine genes in IL-31-treated keratinocytes (PDF 5 kb)

Supplementary Table 3

Extent and timing of skin phenotype in IL-31 Tg mice (PDF 5 kb)

Supplementary Table 4

Lymphoid and myeloid cell development is normal in IL-31RA-deficient mice (PDF 6 kb)

Supplementary Note (XLS 31 kb)

Supplementary Methods (PDF 5 kb)

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Dillon, S., Sprecher, C., Hammond, A. et al. Interleukin 31, a cytokine produced by activated T cells, induces dermatitis in mice. Nat Immunol 5, 752–760 (2004) doi:10.1038/ni1084

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