INFLAMMATION Itching for a New Cytokine

Activation of the immune system can guard against pathogens that cause disease, but the same mechanisms gone awry can lead to autoimmune diseases or allergies. For instance, atopic dermatitis, an inflammatory skin disease that is frequently associated with hay fever or asthma, appears to involve abnormal cytokine production by T helper type 2 (T_H2) cells. Dillon et al. cloned a gp-130-like cytokine receptor with four splice variants, which they called IL-31RAv1 to 4. When IL-31RA was expressed in a lymphoid cell line together with OSMR (oncostatin M receptor), a receptor in the same family, the cells proliferated in response to conditioned medium from activated T cells. The authors identified cDNA from an activated T cell library that encoded a novel 164-amino acid protein that also stimulated proliferation. The protein, which they called IL-31, activated STATs (signal transducers and activators of transcription) in cells transfected with OSMR and either IL-31RAv3 or IL-31RAv4. IL-31 was expressed in activated T cells, particularly T_H2 cells. Transgenic mice that overexpressed mouse IL-31 under the control of a lymphocyte-specific promoter developed pruritis and hair loss, as did mice to whom IL-31 was administered by osmotic pump. In a mouse model of airway hyperresponsiveness, exposure of presensitized mice to antigen stimulated IL-31RA expression in lung; when this response was compared in two mouse strains with different susceptibility to T_H2-mediated diseases, the increase in IL-31RA expression was greater in the more susceptible strain. If IL-31 is involved in mediating dermatitis and hyperresponsive airway disease, its identification and characterization may lead to more effective strategies for preventing and treating these disorders.

S. R Dillon, C. Sprecher, A. Hammond, J. Bilsborough, M. Rosenfeld-Franklin, S. R. Presnell, H. S. Haugen, M. Maurer, B. Harder, J. Johnston, S. Bort, S. Mudri, J. L. Kuijper, T. Bukowski, P. Shea, D. L. Dong, M. Dasovich, F. J. Grant, L. Lockwood, S. D. Levin, C. LeCiel, K. Waggie, H. Day, S. Topouzis, J. Kramer, R. Kuestner, Z. Chen, D. Foster, J. Parrish-Novak, J. A. Gross, Interleukin 31, a cytokine produced by activated T cells, induces dermatitis in mice. Nat. Immunol. 5, 752-760 (2004). [Online Journal]