Human IL-31 is induced by IL-4 and promotes T_H2-driven inflammation

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• 作者：Bryony Stott ; Paul Lavender ; Sarah Lehmann ; Davide Pennino ; Stephen Durham ; Carsten B. Schmidt-Weber
• 关键词：Allergic airway inflammation ; TH2 cells ; IL-31 ; IL-4 ; normal human bronchial epithelial cells ; IL-33 ; chromatin immunoprecipitation
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2013
• 出版时间：August, 2013
• 年：2013
• 卷：132
• 期：2
• 页码：446-454.e5
• 全文大小：1289 K

文摘

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Background

The pruritic cytokine IL-31 has been shown to be expressed by murine activated effector T Lymphocytes of a T_H2 phenotype. Like IL-17 and IL-22, IL-31 is a tissue-signaling cytokine the receptor of which is mainly found on nonimmune cells. An overabundance of IL-31 has been shown in patients with atopic disorders, including dermatitis, as well as asthma, and therefore represents a promising drug target, although its regulation in the context of the human T_H2 clusters is not yet known.

Objective

We sought to address the gene regulation of human IL-31 and to test whether IL-31 possesses a similar proallergic function as members of the human T_H2 cytokine family, such as IL-4, IL-5, and IL-13.

Methods

Polyclonal and purified protein derivative of tuburculin-specific T-cell clones were generated. T_H phenotype was determined, and IL-31 was measured by means of ELISA. Gene expression of primary bronchial epithelial cells treated with IL-31 was also measured.

Results

IL-31 was expressed by all of the T_H2 clones and not by T_H1, T_H17, or T_H22. This expression was dependent on autocrine IL-4 expression from these clones because it could be reduced if blocking antibodies to IL-4 were present. Interestingly, T_H1 clones were able to express IL-31 if IL-4 was added to culture. This IL-31 expression was transient and did not affect the phenotype of the T_H1 clones. IL-31 was able to induce proinflammatory genes, such as CCL2 and granulocyte colony-stimulating factor.

Conclusion

IL-31 is not a T_H2 cytokine in the classical sense but is likely to be expressed by a number of cells in an allergic situation in which IL-4 is present and possibly contribute to the allergic reaction.