The Journal of Experimental Medicine
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Published online 23 February 2004 doi:10.1084/jem.20031482
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 199, Number 5, 731-736
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Brief Definitive Report

 Spontaneous Development of Psoriasis in a New Animal Model Shows an Essential Role for Resident T Cells and Tumor Necrosis Factor-{alpha}

Onur Boyman1, Hans Peter Hefti1, Curdin Conrad1, Brian J. Nickoloff2, Mark Suter3, and Frank O. Nestle1

1 Department of Dermatology, University Hospital of Zurich, CH-8091 Zurich, Switzerland
2 Skin Cancer Research Program, Loyola University Medical Center, Cardinal Bernardin Cancer Center, Maywood, IL 60153
3 Institute of Virology, University of Zurich, CH-8057 Zurich, Switzerland

Address correspondence to Frank O. Nestle, Dept. of Dermatology, University Hospital of Zurich, Gloriastrasse 31, 8091 Zurich, Switzerland. Phone: 41-1-255-2533; Fax: 41-1-255-4346; email: nestle{at}derm.unizh.ch

Psoriasis is a common T cell–mediated autoimmune disorder where primary onset of skin lesions is followed by chronic relapses. Progress in defining the mechanism for initiation of pathological events has been hampered by the lack of a relevant experimental model in which psoriasis develops spontaneously. We present a new animal model in which skin lesions spontaneously developed when symptomless prepsoriatic human skin was engrafted onto AGR129 mice, deficient in type I and type II interferon receptors and for the recombination activating gene 2. Upon engraftment, resident human T cells in prepsoriatic skin underwent local proliferation. T cell proliferation was crucial for development of a psoriatic phenotype because blocking of T cells led to inhibition of psoriasis development. Tumor necrosis factor-{alpha} was a key regulator of local T cell proliferation and subsequent disease development. Our observations highlight the importance of resident T cells in the context of lesional tumor necrosis factor-{alpha} production during development of a psoriatic lesion. These findings underline the importance of resident immune cells in psoriasis and will have implications for new therapeutic strategies for psoriasis and other T cell–mediated diseases.

Key Words: autoimmunity • immunotherapy • inflammation • mouse model • skin

The online version of this article includes supplemental material.

H.P. Hefti and C. Conrad contributed equally to this work.

O. Boyman's present address is Dept. of Immunology, IMM4, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037.

H.P. Hefti's present address is Institute of Virology, University of Zurich, Winterthurerstrasse 266, CH-8057 Zurich, Switzerland.

This work was presented in part at the annual meetings 2002 of the Society of Investigative Dermatology, European Society of Dermatological Research, and the Third International Congress on Psoriasis.


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