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| Resolution of psoriasis upon blockade of IL-15 biological activity in a xenograft mouse model |
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| Author(s): Villadsen LS, Schuurman J, Beurskens F, Dam TN, Dagnaes-Hansen F, Skov L, Rygaard J, Voorhorst-Ogink MM, Gerritsen AF, van Dijk MA, Parren PWHI, Baadsgaard O, van de Winkel JGJ |
| Source: JOURNAL OF CLINICAL INVESTIGATION Volume: 112 Issue: 10 Pages: 1571-1580 Published: NOV 2003 |
| Times Cited: 73 References: 42 |
| Abstract: Psoriasis is a chronic inflammatory disease of the skin characterized by epidermal hyperplasia, dermal angiogenesis, infiltration of activated T cells, and increased cytokine levels. One of these cytokines, IL-15, triggers inflammatory cell recruitment, angiogenesis, and production of other inflammatory cytokines, including IFN-gamma, TNF-alpha, and IL-17, which are all upregulated in psoriatic lesions. To investigate the role of IL-15 in psoriasis, we generated mAb's using human immunoglobulin-transgenic mice. One of the IL-15-specific antibodies we generated, 146B7, did not compete with IL-15 for binding to its receptor but potently interfered with the assembly of the IL-15 receptor alpha, beta, gamma complex. This antibody effectively blocked IL-15-induced T cell proliferation and monocyte TNF-alpha release in vitro. In a human psoriasis xenograft model, antibody 146B7 reduced the severity of psoriasis, as measured by epidermal thickness, grade of parakeratosis, and numbers of inflammatory cells and cycling keratinocytes. These results obtained with this IL-15-specific mAb support an important role for IL-15 in the pathogenesis of psoriasis. |
| Document Type: Article |
| Language: English |
| Reprint Address: Schuurman, J (reprint author), Genmab BV, Jenalaan 18D, NL-3584 CK Utrecht, Netherlands |
Addresses:
1. Genmab BV, NL-3584 CK Utrecht, Netherlands
2. Univ Copenhagen, Gentofte Hosp, Dept Dermatol, Copenhagen, Denmark
3. Univ Aarhus, Marselisborg Hosp, Dept Dermatol, Aarhus, Denmark
4. Univ Aarhus, Dept Med Microbiol, Aarhus, Denmark
5. Copenhagen Univ Hosp, Bartholin Inst, Copenhagen, Denmark
6. Genmab AS, Copenhagen, Denmark
7. Univ Utrecht, Med Ctr, Dept Immunol, Utrecht, Netherlands |
| Publisher: AMER SOC CLINICAL INVESTIGATION INC, 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA |
| Subject Category: Medicine, Research & Experimental |
| IDS Number: 743NU |
| ISSN: 0021-9738 |
| DOI: 10.1172/JCI200318986 |
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