Atopic dermatitis and skin diseaseA sensory neuron–expressed IL-31 receptor mediates T helper cell–dependent itch: Involvement of TRPV1 and TRPA1
Section snippets
Materials
Recombinant mouse IL-31 was provided by ZymoGenetics (Seattle, Wash). For details, see the Methods section in this article's Online Repository at www.jacionline.org.
Patients
Patients and healthy control subjects were included after providing written informed consent within a study protocol approved by the ethics committees of the University Hospital Muenster, Heinrich-Heine-University Düsseldorf, and University Hospital Göttingen, Germany. For details, see the Methods section in this article's Online
Production of IL-31 by human TH2 cells
Several studies have demonstrated that IL-31 is expressed by skin-homing TH2 cells during inflammation, most notably in patients with AD.6, 7, 19, 23 No study has systematically compared expression levels of IL-31 in all potentially relevant immune and permanent skin cells involved in AD. Using qPCR,20 we compared expression levels of IL-31 and its receptor, IL-31RA, in various immune and permanent skin cells of patients with AD and psoriasis. Skin specimens were obtained from healthy donors
Discussion
The resistance of prevalent pruritic diseases to antihistamines, as exemplified by AD, argues strongly for the existence of histamine-independent pruritic pathways that are important targets for therapy of chronic itch.11, 12, 13 We demonstrate that IL-31 induces itch by directly activating IL-31RA on TRPV1+/TRPA1+ sensory nerves in the skin. We show that TH2 cells are the predominant cellular source of IL-31 and that the number and activation of TH2 cells, as well as IL-31 levels, are
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Supported by grants from the National Institutes of Health (NIH)/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS; AR059402), Deutsche Forschungsgemeinschaft (DFG; Ste1014/2-2), IZKF Muenster (STE3/034/07), and CE.R.I.E.S. Paris (to M.S.); NIH NS14627 (to A.B.); NIH AR057194 (to E.C.); DFG Ce165/1-1 (to F.C.); DFG Ke1672/1-1 (to C.K.); and DFG (Ho2092/4-1) and DFG-FOR729 (Ho2092/5-2; to B.H.).
Disclosure of potential conflict of interest: C. Kempkes, M. Feld, and B. Homey have been supported by one or more grants from Deutsche Forschungsgemaeinschaft (the German Research Foundation). A. Ikoma is employed by Galderma Japan. S. R. Dillon has received research support from and is employed by ZymoGenetics (a wholly owned subsidiary of Bristol-Meyers Squibb) and owns stock/stock options in Bristol-Meyers Squibb. A. Basbaum has received research support from the National Institutes of Health (NIH). M. Steinhoff has received research support from the NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and BMS/Zymogenetics. The rest of the authors declare that they have no relevant conflicts of interest.
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These authors contributed equally to this work.
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Co-senior authors.
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Also affiliated with the Clinic of Dermatology and Allergology, University Medical Center, Goettingen, Germany.