CD8(+) T cells mediate RAS-induced psoriasis-like skin inflammation through IFN-γ.
CD8(+) T cells mediate RAS-induced psoriasis-like skin inflammation through IFN-γ.
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DOI：
10.1038/jid.2012.390
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发表时间：
2013-04
影响因子：
6.5
通讯作者：
Glick, Adam B.
中科院分区：
文献类型：
--
作者：
Gunderson, Andrew J.;Mohammed, Javed;Horvath, Frank J.;Podolsky, Michael A.;Anderson, Cherie R.;Glick, Adam B.
The RAS signaling pathway is constitutively activated in psoriatic keratinocytes. We expressed activated H-RASV12G in suprabasal keratinocytes of adult mice and observed rapid development of a psoriasis-like skin phenotype characterized by basal keratinocyte hyperproliferation, acanthosis, hyperkeratosis, intraepidermal neutrophil microabscesses and increased Th1/Th17 and Tc1/Tc17 skin infiltration. The majority of skin infiltrating CD8+ T cells co-expressed IFN-γ and IL-17A. When RAS was expressed on a Rag1−/− background, microabscess formation, iNOS expression and keratinocyte hyperproliferation were suppressed. Depletion of CD8+ but not CD4+ T cells reduced cutaneous and systemic inflammation, the RAS-induced increase in cutaneous Th17 and IL-17+ γΔ T cells, and epidermal hyperproliferation to levels similar to a Rag1−/− background. Reconstitution of Rag1−/− inducible RAS mice with purified CD8+ T cells restored microabscess formation and epidermal hyperproliferation. Neutralization of IFN-γ but not IL-17A in CD8+ T cell reconstituted Rag1−/− mice expressing RAS blocked CD8-mediated skin inflammation, iNOS expression and keratinocyte hyperproliferation. These results show for that CD8+ T cells can orchestrate skin inflammation with psoriasis-like pathology in response to constitutive RAS activation in keratinocytes, and this is primarily mediated through IFN-γ.
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DOI：
10.4049/jimmunol.181.7.4733
发表时间：
2008-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Kryczek I;Bruce AT;Gudjonsson JE;Johnston A;Aphale A;Vatan L;Szeliga W;Wang Y;Liu Y;Welling TH;Elder JT;Zou W
通讯作者：
Zou W
影响因子：
82.9
作者：
Conrad, Curdin;Boyman, Onur;Nestle, Frank O.
通讯作者：
Nestle, Frank O.
DOI：
10.1084/jem.184.5.2007
发表时间：
1996-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bruch-Gerharz D;Fehsel K;Suschek C;Michel G;Ruzicka T;Kolb-Bachofen V
通讯作者：
Kolb-Bachofen V
影响因子：
5.4
作者：
Huber, Magdalena;Heink, Sylvia;Lohoff, Michael
通讯作者：
Lohoff, Michael
影响因子：
6.5
作者：
Guenther, Claudia;Carballido-Perrig, Nicole;Biedermann, Tilo
通讯作者：
Biedermann, Tilo