EUNIPPSO: European union network for investigation of the pathogenesis of psoriasis vulgaris

• Research unit: EU RFP
• Project number: 97.0264

Key words (English)

Psoriasis; H. Saimiri; T-lymphocytes; animal model

Alternative project number (English)

EU project number: FMRXCT980205

Research programs (English)

EU-programme: 4. Frame Research Programme - 10.1 Stimulation of training and mobility

Short description (English)

See abstract

Partners and International Organizations (English)

Coordinator: Christian-
Albrechts-Universität zu Kiel (D)

Abstract (English)

We asked whether disease development in psoriasis is depending on passenger leukocytes or an intrinsic property of non-involved (PN) psoriatic skin. This question was addressed in a new mouse model (established in collaboration with M. Suter, Vetereinary Hospital, Zürich) using PN skin transplanted onto AGR 129 mice. AGR 129 mice are deficient in type I (A 129) and type II (G 129) interferon receptors in addition to lacking functional T- and B-cells (R 129; Rag-/-). We observed spontaneous conversion of PN skin to psoriatic (PP) skin in 31 out of 31 skin grafts transplanted onto AGR mice after 6-8 weeks. This is in contrast to previously reported models which necessitated the injection of immunocytes to induce a psoriatic phenotype. Skin grafts from healthy donors (n=6) transplanted onto AGR 129 mice served as negative control. PN to PP skin conversion was shown on the macroscopic as well as microscopic level. Typical clinical features of converted skin included erythema, infiltration and scaling. Histology demonstrated pronounced psoriasiform hyperplasia with thin suprapapillary plates overlying dilated vessels of the papillary dermis. There was pronounced acanthosis, papillomatosis and parakeratosis. Premature epidermal differentiation was indicated by an increase of involucrin positive cell layers as well keratin 16 expression throughout the epidermis. Activated keratinocytes expressed high levels of ICAM-1 and HLA-DR. Strong suprabasal expression of Ki67 indicated a hyperproliferative epidermal compartment. Persistent presence of CD3, positive T cells in skin grafts (up to 8 weeks) along with highly increased numbers of HLA-DR positive dendritic cells provided a cellular basis for an activated dermal immune compartment.
Conversion of clinically uninvolved psoriatic skin to psoriasis in AGR mice may be caused by a Koebner phenomenon in pre-conditioned skin related to surgery during transplantation. Our model indicates that the conversion of normal appearing skin to a disease specific phenotype is an intrinsic property of skin in patients with psoriasis and independent of the recruitment of passenger immunocytes.

References in databases (English)

Swiss Database: Euro-DB of the
State Secretariat for Education and Research
Hallwylstrasse 4
CH-3003 Berne, Switzerland
Tel. [phone]
Swiss Project-Number: 97.0264