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CD8+ T Cells Mediate RAS-Induced Psoriasis-Like Skin Inflammation through IFN-γ

Gunderson, Andrew J. ; Mohammed, Javed ; Horvath, Frank J. ; Podolsky, Michael A. ; Anderson, Cherie R. ; Glick, Adam B.

Journal of investigative dermatology, 2013-04, Vol.133 (4), p.955-963 [Periódico revisado por pares]

United States: Elsevier Inc

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CD8+ T Cells Mediate RAS-Induced Psoriasis-Like Skin Inflammation through IFN-γ
Autor: Gunderson, Andrew J. ; Mohammed, Javed ; Horvath, Frank J. ; Podolsky, Michael A. ; Anderson, Cherie R. ; Glick, Adam B.
Assuntos: Abscess - immunology ; Abscess - pathology ; Animals ; CD8-Positive T-Lymphocytes - immunology ; CD8-Positive T-Lymphocytes - pathology ; Cell Proliferation ; Dermatitis - genetics ; Dermatitis - immunology ; Dermatitis - pathology ; Epidermis - immunology ; Epidermis - metabolism ; Epidermis - pathology ; Female ; Interferon-gamma - immunology ; Interferon-gamma - metabolism ; Interleukin-17 - genetics ; Interleukin-17 - immunology ; Interleukin-17 - metabolism ; Keratinocytes - immunology ; Keratinocytes - metabolism ; Keratinocytes - pathology ; Male ; Mice ; Mice, Transgenic ; Neutrophils - immunology ; Neutrophils - pathology ; Phenotype ; Proto-Oncogene Proteins p21(ras) - genetics ; Proto-Oncogene Proteins p21(ras) - immunology ; Proto-Oncogene Proteins p21(ras) - metabolism ; Psoriasis - genetics ; Psoriasis - immunology ; Psoriasis - pathology ; Signal Transduction - immunology ; Th1 Cells - immunology ; Th1 Cells - pathology ; Th17 Cells - immunology ; Th17 Cells - pathology
É parte de: Journal of investigative dermatology, 2013-04, Vol.133 (4), p.955-963
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
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Descrição: 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 T helper type 1 (Th1)/Th17 and T cell type 1 (Tc1)/Tc17 skin infiltration. The majority of skin-infiltrating CD8+ T cells coexpressed IFN-γ and IL-17A. When RAS was expressed on a Rag1-/- background, microabscess formation, inducible nitric oxide synthase 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 of IL-17A, in CD8+ T-cell-reconstituted Rag1-/- mice expressing RAS blocked CD8-mediated skin inflammation, inducible nitric oxide synthase expression, and keratinocyte hyperproliferation. These results show 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.
Editor: United States: Elsevier Inc
Idioma: Inglês

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CD8+ T Cells Mediate RAS-Induced Psoriasis-Like Skin Inflammation through IFN-γ

Gunderson, Andrew J. ; Mohammed, Javed ; Horvath, Frank J. ; Podolsky, Michael A. ; Anderson, Cherie R. ; Glick, Adam B.

United States: Elsevier Inc

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