A 9-centimorgan interval of chromosome 10 controls the T cell-dependent psoriasiform skin disease and arthritis in a murine psoriasis model
(2008) In Journal of Immunology 180(8). p.5520-5529- Abstract
- Psoriasis is a complex genetic disease of unresolved pathogenesis with both heritable and environmental factors contributing to onset and severity. In addition to a disfiguring skin inflammation, approximately 10-40% of psoriasis patients suffer from destructive joint involvement. Previously, we reported that the CD18 hypomorphic PL/J mouse carrying a mutation resulting in reduced expression of the common chain of beta(2) integrins (CD11/CD18) spontaneously develops a skin disease that closely resembles human psoriasis. In contrast, the same mutation on C57BL/6J background did not demonstrate this phenotype. By a genome-wide linkage analysis, two major loci were identified as contributing to the development of psoriasiform dermatitis under... (More)
- Psoriasis is a complex genetic disease of unresolved pathogenesis with both heritable and environmental factors contributing to onset and severity. In addition to a disfiguring skin inflammation, approximately 10-40% of psoriasis patients suffer from destructive joint involvement. Previously, we reported that the CD18 hypomorphic PL/J mouse carrying a mutation resulting in reduced expression of the common chain of beta(2) integrins (CD11/CD18) spontaneously develops a skin disease that closely resembles human psoriasis. In contrast, the same mutation on C57BL/6J background did not demonstrate this phenotype. By a genome-wide linkage analysis, two major loci were identified as contributing to the development of psoriasiform dermatitis under the condition of low CD18 expression. Using a congenic approach, we now demonstrate that the introduction of a 9-centimorgan fragment of chromosome 10 derived from the PL/J strain into the disease-resistant CD18 hypomorphic C57BL/6J was promoting the development of psoriasiform skin disease and notably also arthritis. We therefore designated this locus psoriasiform skin disease-associated locus 1 (PSD1). High numbers of CD4(+) T cells and TNF-alpha producing macrophages were detected both in inflamed skin and joints in these congenic mice, with a complete resolution upon TNF-alpha inhibitor therapy or depletion of CD4(+) T cells. For the first time, we have identified a distinct genetic element that contributes to the T cell-dependent development of both psoriasiform skin disease and associated arthritis. This congenic model will be suitable to further investigations of genetic and molecular pathways that cause psoriasiform dermatitis and arthritis, and it may also be relevant for other autoimmune diseases. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1254673
- author
- Wang, Honglin ; Kess, Daniel ; Lindqvist, Anna-Karin LU ; Peters, Thorsten ; Sindrilaru, Anca ; Wlaschek, Meinhard ; Blakytny, Robert ; Holmdahl, Rikard LU and Scharffetter-Kochanek, Karin
- organization
- publishing date
- 2008
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Immunology
- volume
- 180
- issue
- 8
- pages
- 5520 - 5529
- publisher
- American Association of Immunologists
- external identifiers
-
- wos:000257506900042
- scopus:45949098797
- ISSN
- 1550-6606
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Medical Inflammation Research (013212019)
- id
- 430190f2-2588-451a-977b-88fe3c43a598 (old id 1254673)
- alternative location
- http://www.jimmunol.org/cgi/content/abstract/180/8/5520
- date added to LUP
- 2016-04-01 14:30:47
- date last changed
- 2022-01-28 00:57:31
@article{430190f2-2588-451a-977b-88fe3c43a598,
abstract = {{Psoriasis is a complex genetic disease of unresolved pathogenesis with both heritable and environmental factors contributing to onset and severity. In addition to a disfiguring skin inflammation, approximately 10-40% of psoriasis patients suffer from destructive joint involvement. Previously, we reported that the CD18 hypomorphic PL/J mouse carrying a mutation resulting in reduced expression of the common chain of beta(2) integrins (CD11/CD18) spontaneously develops a skin disease that closely resembles human psoriasis. In contrast, the same mutation on C57BL/6J background did not demonstrate this phenotype. By a genome-wide linkage analysis, two major loci were identified as contributing to the development of psoriasiform dermatitis under the condition of low CD18 expression. Using a congenic approach, we now demonstrate that the introduction of a 9-centimorgan fragment of chromosome 10 derived from the PL/J strain into the disease-resistant CD18 hypomorphic C57BL/6J was promoting the development of psoriasiform skin disease and notably also arthritis. We therefore designated this locus psoriasiform skin disease-associated locus 1 (PSD1). High numbers of CD4(+) T cells and TNF-alpha producing macrophages were detected both in inflamed skin and joints in these congenic mice, with a complete resolution upon TNF-alpha inhibitor therapy or depletion of CD4(+) T cells. For the first time, we have identified a distinct genetic element that contributes to the T cell-dependent development of both psoriasiform skin disease and associated arthritis. This congenic model will be suitable to further investigations of genetic and molecular pathways that cause psoriasiform dermatitis and arthritis, and it may also be relevant for other autoimmune diseases.}},
author = {{Wang, Honglin and Kess, Daniel and Lindqvist, Anna-Karin and Peters, Thorsten and Sindrilaru, Anca and Wlaschek, Meinhard and Blakytny, Robert and Holmdahl, Rikard and Scharffetter-Kochanek, Karin}},
issn = {{1550-6606}},
language = {{eng}},
number = {{8}},
pages = {{5520--5529}},
publisher = {{American Association of Immunologists}},
series = {{Journal of Immunology}},
title = {{A 9-centimorgan interval of chromosome 10 controls the T cell-dependent psoriasiform skin disease and arthritis in a murine psoriasis model}},
url = {{http://www.jimmunol.org/cgi/content/abstract/180/8/5520}},
volume = {{180}},
year = {{2008}},
}