A 9-centimorgan interval of chromosome 10 controls the T cell-dependent psoriasiform skin disease and arthritis in a murine psoriasis model

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A 9-centimorgan interval of chromosome 10 controls the T cell-dependent psoriasiform skin disease and arthritis in a murine psoriasis model. / Wang, Honglin; Kess, Daniel; Lindqvist, Anna-Karin; Peters, Thorsten; Sindrilaru, Anca; Wlaschek, Meinhard; Blakytny, Robert; Holmdahl, Rikard; Scharffetter-Kochanek, Karin.

In: Journal of Immunology, Vol. 180, No. 8, 2008, p. 5520-5529.

Research output: Contribution to journalArticle

Harvard

Wang, H, Kess, D, Lindqvist, A-K, Peters, T, Sindrilaru, A, Wlaschek, M, Blakytny, R, Holmdahl, R & Scharffetter-Kochanek, K 2008, 'A 9-centimorgan interval of chromosome 10 controls the T cell-dependent psoriasiform skin disease and arthritis in a murine psoriasis model', Journal of Immunology, vol. 180, no. 8, pp. 5520-5529.

APA

Wang, H., Kess, D., Lindqvist, A-K., Peters, T., Sindrilaru, A., Wlaschek, M., ... Scharffetter-Kochanek, K. (2008). A 9-centimorgan interval of chromosome 10 controls the T cell-dependent psoriasiform skin disease and arthritis in a murine psoriasis model. Journal of Immunology, 180(8), 5520-5529.

CBE

Wang H, Kess D, Lindqvist A-K, Peters T, Sindrilaru A, Wlaschek M, Blakytny R, Holmdahl R, Scharffetter-Kochanek K. 2008. A 9-centimorgan interval of chromosome 10 controls the T cell-dependent psoriasiform skin disease and arthritis in a murine psoriasis model. Journal of Immunology. 180(8):5520-5529.

MLA

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Author

Wang, Honglin ; Kess, Daniel ; Lindqvist, Anna-Karin ; Peters, Thorsten ; Sindrilaru, Anca ; Wlaschek, Meinhard ; Blakytny, Robert ; Holmdahl, Rikard ; Scharffetter-Kochanek, Karin. / A 9-centimorgan interval of chromosome 10 controls the T cell-dependent psoriasiform skin disease and arthritis in a murine psoriasis model. In: Journal of Immunology. 2008 ; Vol. 180, No. 8. pp. 5520-5529.

RIS

TY - JOUR

T1 - A 9-centimorgan interval of chromosome 10 controls the T cell-dependent psoriasiform skin disease and arthritis in a murine psoriasis model

AU - Wang, Honglin

AU - Kess, Daniel

AU - Lindqvist, Anna-Karin

AU - Peters, Thorsten

AU - Sindrilaru, Anca

AU - Wlaschek, Meinhard

AU - Blakytny, Robert

AU - Holmdahl, Rikard

AU - Scharffetter-Kochanek, Karin

N1 - 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)

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

M3 - Article

VL - 180

SP - 5520

EP - 5529

JO - Journal of immunology (Baltimore, Md. : 1950)

JF - Journal of immunology (Baltimore, Md. : 1950)

SN - 1550-6606

IS - 8

ER -