Psoriasis genomics: analysis of proinflammatory (type 1) gene expression in large plaque (Western) and small plaque (Asian) psoriasis vulgaris

Lew, Wook; Lee, E; Krueger, James G.

doi:10.1111/j.0007-0963.2004.05891.x

Cited by 62 publications

(58 citation statements)

References 35 publications

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“…This cytokine expression pattern is similar to the inflammatory response in human psoriatic plaques and therefore validates the CD18 hypo PL/J psoriasis model (44,45). Although skin gd T cells have previously been reported to primarily produce IL-17, our IF analyses of CD18 hypo PL/J skin sections convincingly demonstrated that dermal gd T cells significantly contributed to IL-17, IL-22, and TNF-a production.…”

Section: Discussionsupporting

confidence: 84%

Reduction of CD18 Promotes Expansion of Inflammatory γδ T Cells Collaborating with CD4+ T Cells in Chronic Murine Psoriasiform Dermatitis

Gatzka

Hainzl

Peters

et al. 2013

The Journal of Immunology

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IL-17 is a critical factor in the pathogenesis of psoriasis and other inflammatory diseases. The impact of γδ T cells, accounting for an important source of IL-17 in acute murine IL-23– and imiquimod-induced skin inflammation, in human psoriasis is still unclear. Using the polygenic CD18hypo PL/J psoriasis mouse model spontaneously developing chronic psoriasiform dermatitis due to reduced CD18/β2 integrin expression to 2–16% of wild-type levels, we investigated in this study the influence of adhesion molecule expression on generation of inflammatory γδ T cells and analyzed the occurrence of IL-17–producing γδ and CD4+ T cells at different disease stages. Severity of CD18hypo PL/J psoriasiform dermatitis correlated with a loss of skin-resident Vγ5+ T cells and concurrent skin infiltration with IL-17+, IL-22+, and TNF-α+ γδTCRlow cells preceded by increases in Vγ4+ T cells in local lymph nodes. In vitro, reduced CD18 levels promoted expansion of inflammatory memory-type γδ T cells in response to IL-7. Similar to IL-17 or IL-23/p19 depletion, injection of diseased CD18hypo PL/J mice with anti-γδTCR Abs significantly reduced skin inflammation and largely eliminated pathological γδ and CD4+ T cells. Moreover, CD18hypo γδ T cells induced allogeneic CD4+ T cell responses more potently than CD18wt counterparts and, upon adoptive transfer, triggered psoriasiform dermatitis in susceptible hosts. These results demonstrate a novel function of reduced CD18 levels in generation of pathological γδ T cells that was confirmed by detection of increases in CD18low γδ T cells in psoriasis patients and may also have implications for other inflammatory diseases.

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Section: Discussionsupporting

confidence: 84%

Reduction of CD18 Promotes Expansion of Inflammatory γδ T Cells Collaborating with CD4+ T Cells in Chronic Murine Psoriasiform Dermatitis

Gatzka

Hainzl

Peters

et al. 2013

The Journal of Immunology

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“…In psoriasis, neutrophils first infiltrate into the dermis at the early phase and later into the epidermis at the chronic phase (6). Moreover, neutrophil chemoattractants, including CXCL1, CXCL8 (also known as IL-8), and leukotriene B 4 (LTB 4 ), are upregulated in psoriatic skin (7,8). A case report documented psoriasis remission during drug-induced agranulocytosis and its reappearance after the recovery of neutrophil numbers in the blood (9), suggesting a critical role of neutrophils in psoriatic skin inflammation.…”

mentioning

confidence: 99%

Interplay between CXCR2 and BLT1 Facilitates Neutrophil Infiltration and Resultant Keratinocyte Activation in a Murine Model of Imiquimod-Induced Psoriasis

Sumida

Yanagida

Kita

et al. 2014

The Journal of Immunology

134

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Psoriasis is an inflammatory skin disease with accelerated epidermal cell turnover. Neutrophil accumulation in the skin is one of the histological characteristics of psoriasis. However, the precise mechanism and role of neutrophil infiltration remain largely unknown. In this article, we show that orchestrated action of CXCR2 and leukotriene B4 receptor BLT1 plays a key role in neutrophil recruitment during the development of imiquimod (IMQ)-induced psoriatic skin lesions in mice. Depletion of neutrophils with anti–Ly-6G Ab ameliorated the disease severity, along with reduced expression of proinflammatory cytokine IL-1β in the skin. Furthermore, CXCR2 and BLT1 coordinately promote neutrophil infiltration into the skin during the early phase of IMQ-induced inflammation. In vitro, CXCR2 ligands augment leukotriene B4 production by murine neutrophils, which, in turn, amplifies chemokine-mediated neutrophil chemotaxis via BLT1 in autocrine and/or paracrine manners. In agreement with the increased IL-19 expression in IMQ-treated mouse skin, IL-1β markedly upregulated expression of acanthosis-inducing cytokine IL-19 in human keratinocytes. We propose that coordination of chemokines, lipids, and cytokines with multiple positive feedback loops might drive the pathogenesis of psoriasis and, possibly, other inflammatory diseases as well. Interference to this positive feedback or its downstream effectors could be targets of novel anti-inflammatory treatment.

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“…106,107 Mice lacking IRF2 are hyper-responsive to IFN-a/b, dramatically overexpress genes induced by type I IFN and develop inflammatory dermatological manifestations involving CD8 þ T cells. 108 Numerous lines of evidence suggest that pathways influenced by IFNs are dysregulated in multiple autoimmune diseases, including SLE, PS, AITD, Crohn's, RA and spondyloarthropathy, [109][110][111][112][113] supporting a potential role for genes such as IRF2.…”

mentioning

confidence: 99%

Familial aggregation and linkage analysis of autoantibody traits in pedigrees multiplex for systemic lupus erythematosus

et al. 2006

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Autoantibodies are clinically relevant biomarkers for numerous autoimmune disorders. The genetic basis of autoantibody production in systemic lupus erythematosus (SLE) and other autoimmune diseases is poorly understood. In this study, we characterized autoantibody profiles in 1506 individuals from 229 multiplex SLE pedigrees. There was strong familial aggregation of antinuclear antibodies (ANAs), anti-double-stranded DNA (dsDNA), anti-La/SSB, anti-Ro/SSA, anti-Sm, antinRNP (nuclear ribonucleoprotein), IgM antiphospholipid (aPL) antibodies (Abs) and rheumatoid factor (RF) across these families enriched for lupus. We performed genome-wide linkage analyses in an effort to map genes that contribute to the production of the following autoantibodies: Ro/SSA, La/SSB, nRNP, Sm, dsDNA, RF, nuclear and phospholipids. Using an approach to minimize false positives and adjust for multiple comparisons, evidence for linkage was found to anti-La/SSB Abs on chromosome 3q21 (adjusted P ¼ 1.9 Â 10 À6 ), to anti-nRNP and/or anti-Sm Abs on chromosome 3q27 (adjusted P ¼ 3.5 Â 10 À6 ), to anti-Ro/SSA and/or anti-La/SSB Abs on chromosome 4q34-q35 (adjusted P ¼ 3.4 Â 10 À4 ) and to antiIgM aPL Abs on chromosome 13q14 (adjusted P ¼ 2.3 Â 10 À4). These results support the hypothesis that autoantibody production is a genetically complex trait. Identification of the causative alleles will advance our understanding of critical molecular mechanisms that underlie SLE and perhaps other autoimmune diseases.

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Psoriasis genomics: analysis of proinflammatory (type 1) gene expression in large plaque (Western) and small plaque (Asian) psoriasis vulgaris

Cited by 62 publications

References 35 publications

Reduction of CD18 Promotes Expansion of Inflammatory γδ T Cells Collaborating with CD4+ T Cells in Chronic Murine Psoriasiform Dermatitis

Reduction of CD18 Promotes Expansion of Inflammatory γδ T Cells Collaborating with CD4+ T Cells in Chronic Murine Psoriasiform Dermatitis

Interplay between CXCR2 and BLT1 Facilitates Neutrophil Infiltration and Resultant Keratinocyte Activation in a Murine Model of Imiquimod-Induced Psoriasis

Familial aggregation and linkage analysis of autoantibody traits in pedigrees multiplex for systemic lupus erythematosus

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