IL-31: a new link between T cells and pruritus in atopic skin inflammation.
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 T(H)1 and T(H)2 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.


CONCLUSIONS
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.
Sonkoly
Eniko
E
Department of Dermatology, Heinrich-Heine-University, Düsseldorf, Germany.
Muller
Anja
A
Lauerma
Antti I
AI
Pivarcsi
Andor
A
Soto
Hortensia
H
Kemeny
Lajos
L
Alenius
Harri
H
Dieu-Nosjean
Marie-Caroline
MC
Meller
Stephan
S
Rieker
Juliane
J
Steinhoff
Martin
M
Hoffmann
Thomas K
TK
Ruzicka
Thomas
T
Zlotnik
Albert
A
Homey
Bernhard
B
D003876:Dermatitis, Atopic / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D005727:Ganglia, Spinal / Q000378:metabolism; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D008213:Lymphocyte Activation; D011536:Prurigo / Q000276:immunology / Q000378:metabolism; D011537:Pruritus / Q000276:immunology* / Q000378:metabolism / Q000503:physiopathology; D011565:Psoriasis / Q000276:immunology / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation
C502187:IL31 protein, human; C502188:IL31RA protein, human; D007378:Interleukins; D018123:Receptors, Interleukin; D018089:Superantigens