Activation of human eosinophils and epidermal keratinocytes by Th2 cytokine IL-31: Implication for the immunopathogenesis of atopic dermatitis

Phyllis Fung Yi Cheung, Chun Kwok Wong, Amy Wing Yin Ho, Shuiqing Hu, Da Peng Chen, Christopher Wai Kei Lam

Research output: Contribution to journalArticlepeer-review

63 Scopus citations

Abstract

IL-31 is a novel Th type 2 cytokine that can induce pruritus and dermatitis in mice resembling human atopic dermatitis (AD). Eosinophil infiltration in skin lesions is a predominant pathological feature of AD. In the present study, we investigated the effects of IL-31 on the activation of human eosinophils and epidermal keratinocytes. Eosinophils and keratinocytes were cultured either together or separately in the presence or absence of IL-31 stimulation. IL-31 could significantly induce the release of pro-inflammatory cytokines IL-1β, IL-6 and AD-related chemokines CXCL1, CXCL8, CCL2 and CCL18 from eosinophils, via functional cell surface IL-31 receptor. Such induction was further enhanced upon the co-culture of eosinophils and keratinocytes, in which eosinophils were the main source for releasing pro-inflammatory cytokines and chemokines. The presence of transwell inserts in co-culture system demonstrated that the direct interaction between eosinophils and keratinocytes was required for IL-31-induced cytokine and chemokine release. Cell surface expression of adhesion molecule CD18 on eosinophils and intercellular adhesion molecule-1 on keratinocytes was up-regulated in the co-culture, and levels were further enhanced upon IL-31 stimulation. The interaction between eosinophils and keratinocytes under IL-31 stimulation was differentially mediated through intracellular mitogen-activated protein kinases, nuclear factor-κB and phosphatidylinositol 3-kinase-Akt pathways. The above findings suggest a crucial immunopathological role of IL-31 in AD through activation of eosinophils-keratinocytes system.

Original languageEnglish (US)
Pages (from-to)453-467
Number of pages15
JournalInternational Immunology
Volume22
Issue number6
DOIs
StatePublished - Apr 21 2010

Keywords

  • Adhesion molecules
  • Chemokines
  • Eosinophils
  • IL-31
  • Keratinocytes
  • Mitogen-activated protein kinases
  • Signaling molecules

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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