Human IL-31 is induced by IL-4 and promotes TH2-driven inflammation

Abstract

Background: The pruritic cytokine IL-31 has been shown to be expressed by murine activated effector T Lymphocytes of a TH2 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 TH2 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 TH2 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. TH 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 TH2 clones and not by TH1, TH17, or TH22. 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, TH1 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 TH1 clones. IL-31 was able to induce proinflammatory genes, such as CCL2 and granulocyte colony-stimulating factor.

Conclusion: IL-31 is not a TH2 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.

Keywords: Allergic airway inflammation; ChIP; Chromatin immunoprecipitation; EF1a; Elongation factor 1a; FACS; Fluorescence-activated cell sorting; G-CSF; Granulocyte colony-stimulating factor; IL-31; IL-31 receptor α; IL-31RA; IL-33; IL-4; NHBE; Normal human bronchial epithelial cell; PPD; Purified protein derivative of tuburculin; RT-PCR; Real-time PCR; T(H)2 cells; chromatin immunoprecipitation; normal human bronchial epithelial cells.