Abstract
Preliminary observations in a xenogeneic SCID mouse transplantation model indicated that murine epidermis overgrows human dermis from psoriatic skin but not that form normal skin. To investigate the effect of peripheral blood mononuclear cells on the differentiation of murine keratinocytes, we transplanted involved and uninvolved full-thickness skin from patients with psoriasis onto SCID mice and followed this with repeated subcutaneous injections of cells suspended in patient serum. After 6 weeks grafts were analysed morphologically and immunohistochemically. The epidermis in grafts from clinically uninvolved skin appeared normal. The persistence of a psoriasiform epidermis was noted in all grafts from affected sites despite a lack of lymphocytic infiltration. Staining for human and mouse MHC class I antigens revealed the murine origin of keratinocytes forming the psoriasiform epidermis, while the human dermis was retained. Our observations indicate that the defect underlying the pathogenesis of psoriasis is most likely located in the dermal rather than the epidermal compartment. This xenogeneic transplantation model may be useful for future studies of the pathogenesis and treatment of psoriasis.
Similar content being viewed by others
References
Barnstable CJ, Bodmer WF, Brown G, Galfre G, Milstein C, Williams AF, Ziegler A (1978) Production of monoclonal antibodies to group A erythrocytes, HLA and other human cell surface antigens — new tools for genetic analysis. Cell 14: 9–20
Bos JD (1988) The pathomechanisms of psoriasis; the skin immune system and cyclosporin. Br J Dermatol 118: 141–155
Bosma MJ, Carroll AM (1991) The SCID mouse mutant: definition, characterization, and potential uses. Annu Rev Immunol 9: 323–350
Briggaman RA, Wheeler CE (1978) Nude mouse-human skin graft model III. Studies on generalized psoriasis (abstract). J Invest Dermatol 74: 262
Fraki JE, Briggaman RA, Lazarus GS (1980) Transplantation of psoriatic skin onto nude mice. J Invest Dermatol [Suppl] 80: 31–35
Haftek M, Ortonne JP, Staquet MJ, Viac J, Thivolet J (1981 Normal and psoriatic human skin grafts on “nude” mice: morphological and immunological studies. J invest Dermatol 76: 48–52
Hemler ME, Jacobson JG, Strominger JL (1985) Biochemical characterization of VLA-1 and VLA-2: cell surface heterodimers on activated T cells. J Biol Chem 260: 15246–15252
Hemler ME, Huang C; Takada Y, Schwarz L, Strominger JL, Clabby ML (1987) Characterization of the cell surface heterodimer VLA-4 and related peptides. J Biol Chem 262: 11478–11485
Hemler ME, Crouse C, Takada Y, Sonnenberg A (1988) Multiple very late antigen (VLA) heterodimers on platelets. Evidence for distinct VLA-2, VLA-5 (fibronectin receptor) and VLA-6 structures. J Biol Chem 263: 7660–7665
Iizuka H, Adachi K, Halprin K, Levine V (1978) Cyclic AMP accumulation in psoriatic skin: differential responses to histamine, AMP and epinephrine by the uninvolved and involved epidermis. J Invest Dermatol 70: 250–253
Kaufmann R, Frösch D, Westphal C, Weber L, Klein CE (1989) Integrin VLA-3: ultrastructural localization at cell-cell contact sites of human cell cultures. J Cell Biol 109: 1807–1815
Krueger GC (1975) Long-term maintenance of psoriatic human skin on congenitally athymic (nude) mice. J Invest Dermatol 64: 307–312
Mielke V, Sterry W, Kaufmann R (1993) Skin associated lymphatic tissue (SALT) is retained in xenografts of human skin on SCID-mice (abstract). J Invest Dermatol 100: 445
Nepom GT, Ehrlich H (1991) MHC class-II molecules and autoimmunity. Annu Rev. Immunol 9: 493–525
Ozato K, Mayer N, Sachs DH (1982) monoclonal antibodies to mouse major histocompatibility complex antigens. Transplantation 34: 113–120
Rothlein R, Dustin ML, Marlin SD, Springer TA (1986) A human intercellular adhesion molecule (ICAM-1) distinct from LFA-1. J Immunol 137: 1270–1274
Sanchez-Madrid F, Krnzky AM, Ware CF, Robbins E, Strominger JL, Burakoff SJ, Springer TA (1982) Three distinct antigens associated with human T-lymphocyte-mediated cytolysis: LFA-1, LFA-2, and LFA-3. Proc Natl Acad Sci USA 79: 7489–7493
Schmitt-Egenolf M, Boehncke W-H, Eiermann TH, Sterry W (1993) Oligonucleotide typing reveals association of type I psoriasis with the HLA-DRB1*0701/2, -DQA1*0201, -DQB1*0303 extended haplotype. J Invest Dermatol 100: 749–752
Sonnenberg A, Modderman PW, Hogervorst F (1988) Laminin receptor on platelets is the integrin VLA-6. nature 336: 487–489
Werb Z, Tremble PM, Behrendtsen O, Crowley E, Damsky CH (1989) Signal transduction through the fibronectin receptor induces collagenase and stromelysin gene expression. J Cell Biol 109: 877–889
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Boehncke, W.H., Sterry, W., Hainzl, A. et al. Psoriasiform architecture of murine epidermis overlying human psoriatic dermis transplanted onto SCID mice. Arch Dermatol Res 286, 325–330 (1994). https://doi.org/10.1007/BF00402223
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF00402223