Food allergy, dermatologic diseases, and anaphylaxis
IL-31: A new link between T cells and pruritus in atopic skin inflammation

https://doi.org/10.1016/j.jaci.2005.10.033Get rights and content

Background

IL-31 is a novel T-cell–derived cytokine that induces severe pruritus and dermatitis in transgenic mice, and signals through a heterodimeric receptor composed of IL-31 receptor A and oncostatin M receptor.

Objective

To investigate the role of human IL-31 in pruritic and nonpruritic inflammatory skin diseases.

Methods

The expression of IL-31 was analyzed by quantitative real-time PCR in skin samples of healthy individuals and patients with chronic inflammatory skin diseases. Moreover, IL-31 expression was analyzed in nonlesional skin of atopic dermatitis patients after allergen or superantigen exposure, as well as in stimulated leukocytes. The tissue distribution of the IL-31 receptor heterodimer was investigated by DNA microarray analysis.

Results

IL-31 was significantly overexpressed in pruritic atopic compared with nonpruritic psoriatic skin inflammation. Highest IL-31 levels were detected in prurigo nodularis, one of the most pruritic forms of chronic skin inflammation. In vivo, staphylococcal superantigen rapidly induced IL-31 expression in atopic individuals. In vitro, staphylococcal enterotoxin B but not viruses or TH1 and TH2 cytokines induced IL-31 in leukocytes. In patients with atopic dermatitis, activated leukocytes expressed significantly higher IL-31 levels compared with control subjects. IL-31 receptor A showed most abundant expression in dorsal root ganglia representing the site where the cell bodies of cutaneous sensory neurons reside.

Conclusion

Our findings provide a new link among staphylococcal colonization, subsequent T-cell recruitment/activation, and pruritus induction in patients with atopic dermatitis. Taken together, these findings show that IL-31 may represent a novel target for antipruritic drug development.

Section snippets

Patients

Six-millimeter punch biopsies were taken, after obtaining informed consent, from nonlesional (n = 10) or lesional (n = 25) skin of patients with atopic dermatitis, lesional skin of patients with psoriasis (n = 24) or prurigo nodularis (n = 5), and healthy skin (n = 12). Patients with atopic dermatitis were identified according to the criteria defined by Hanifin and Rajka.10 Patients with chronic plaque psoriasis in typical locations were enrolled into the study. Diagnosis of prurigo nodularis

IL-31 is upregulated in atopic dermatitis but not in psoriasis

To analyze the expression of IL-31 in pruritic and nonpruritic chronic inflammatory skin diseases, quantitative real-time PCR analysis was performed of IL-31 mRNA expression in healthy skin (n = 12) and nonlesional (n = 10) and lesional (n = 25) skin of atopic dermatitis as well as lesional skin of patients with psoriasis (n = 24) or prurigo nodularis (n = 5). Our results showed that human IL-31 is significantly (P < .001) upregulated in the pruritic atopic dermatitis but not in the nonpruritic

Discussion

Accumulating evidence indicates that chronic inflammatory skin diseases such as atopic dermatitis and psoriasis are T-cell–mediated diseases.1, 23 Although skin-infiltrating effector memory T cells represent histopathological hallmarks of both atopic dermatitis and psoriasis, their clinical phenotype is distinctly different. Besides other symptoms, atopic skin inflammation is accompanied by severe pruritus,5 whereas psoriatic lesions rarely itch.24

Because the transgenic overexpression of murine

References (38)

  • M.W. Greaves et al.

    Itch: more than skin deep

    Int Arch Allergy Immunol

    (2004)
  • S. Stander et al.

    Pathophysiology of pruritus in atopic dermatitis: an overview

    Exp Dermatol

    (2002)
  • C.F. Wahlgren et al.

    Antipruritic effect of oral cyclosporin A in atopic dermatitis

    Acta Derm Venereol

    (1990)
  • S.R. Dillon et al.

    Interleukin 31, a cytokine produced by activated T cells, induces dermatitis in mice

    Nat Immunol

    (2004)
  • C. Diveu et al.

    Predominant expression of the long isoform of GP130-like (GPL) receptor is required for interleukin-31 signaling

    Eur Cytokine Netw

    (2004)
  • J.M. Hanifin et al.

    Diagnostic criteria of atopic dermatitis

    Acta Derm Venereol

    (1980)
  • U. Darsow et al.

    Airborne and dietary allergens in atopic eczema: a comprehensive review of diagnostic tests

    Clin Exp Dermatol

    (2000)
  • B. Homey et al.

    Cutting edge: the orphan chemokine receptor G protein-coupled receptor-2 (GPR-2, CCR10) binds the skin-associated chemokine CCL27 (CTACK/ALP/ILC)

    J Immunol

    (2000)
  • J. Lee et al.

    Effects of RNA degradation on gene expression analysis of human postmortem tissues

    FASEB J

    (2005)
  • Cited by (0)

    Supported by the European Commission contract QLK4-CT-2001-00366 Chemokine-Atopy (Dr Lauerma, Dr Homey, Dr Alenius, Dr Dieu-Nosjean, Dr Kemeny), the German Research Foundation (SFB503; Dr Homey), the Research Foundation of the Heinrich Heine University (Dr Muller, Dr Hoffmann), the Finnish Foundation of Medicine (Dr Lauerma), and Interdisciplinary Center for Clinical Research (IZKF Münster STE/103/II/04), Sonderforschungsbereich (SFB 293 A14), Centre de recherches et epidermiques et sensorielles (CERIES Paris), Serono Pharm, Germany (Dr Steinhoff).

    These authors contributed equally to the article

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