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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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.
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.
STAT activation by IL-31 in human cells (PDF 4 kb)
Induction of chemokine genes in IL-31-treated keratinocytes (PDF 5 kb)
Extent and timing of skin phenotype in IL-31 Tg mice (PDF 5 kb)
Lymphoid and myeloid cell development is normal in IL-31RA-deficient mice (PDF 6 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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