Abstract
T cells are crucial mediators of the skin damage in psoriasis. We here show that interleukin-21 (IL-21), a T cell–derived cytokine, is highly expressed in the skin of individuals with psoriasis, stimulates human keratinocytes to proliferate and causes epidermal hyperplasia when injected intradermally into mice. In the human psoriasis xenograft mouse model, blockade of IL-21 activity resolves inflammation and reduces keratinocyte proliferation. Blocking IL-21 may represent a new therapeutic strategy in psoriasis.
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Acknowledgements
This work received support from the Fondazione Umberto di Mario and Giuliani SpA, Milan, Italy. It is dedicated to the memory of A. Ribuffo, the Master of the Roman University School of Dermatology.
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R.C. performed cultures with keratinocytes, analyzed cytokine expression and conducted the in vivo experiments; M.L.G. performed the immunohistochemical studies and cultures of primary keratinocytes; M.S., M.E., C.S., M.S., E.B. and V.P. performed flow cytometry staining and western blotting and isolated blood mononuclear cells; E.C., A.M. and L.D. collected skin biopsies; S.C., F.P., T.T.M. and A.C. contributed to supervising parts of the project and writing the paper. G.M. designed research, supervised the project and helped write the manuscript.
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G.M. has filed a patent entitled “Interleukin-21 (IL-21) binding proteins and methods of making and using same” (European Patent Application No. 08425294.9).
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Caruso, R., Botti, E., Sarra, M. et al. Involvement of interleukin-21 in the epidermal hyperplasia of psoriasis. Nat Med 15, 1013–1015 (2009). https://doi.org/10.1038/nm.1995
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DOI: https://doi.org/10.1038/nm.1995
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