title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Allergy and Clinical Immunology, Imperial College, London, United Kingdom.
authors.forename: Bryony
authors.initials: B
authors.lastname: Stott
authors.forename: Paul
authors.initials: P
authors.lastname: Lavender
authors.forename: Sarah
authors.initials: S
authors.lastname: Lehmann
authors.forename: Davide
authors.initials: D
authors.lastname: Pennino
authors.forename: Stephen
authors.initials: S
authors.lastname: Durham
authors.forename: Carsten B
authors.initials: CB
authors.lastname: Schmidt-Weber
mesh_terms: D000818:Animals; D001980:Bronchi; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004847:Epithelial Cells; D005786:Gene Expression Regulation; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology* / Q000378:metabolism; D007249:Inflammation / Q000276:immunology* / Q000378:metabolism; D018793:Interleukin-13 / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015848:Interleukin-5 / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D016207:Cytokines; C502187:IL31 protein, human; C508598:IL4 protein, human; D018793:Interleukin-13; D015848:Interleukin-5; D007378:Interleukins; D015847:Interleukin-4
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