CD69, HLA-DR and the IL-2R Identify Persistently Activated T Cells in Psoriasis Vulgaris Lesional Skin: Blood and Skin Comparisons by Flow Cytometry

Ferenczi, Katalin; Burack, Lauren H.; M, Pope; Krueger, James G.; Austin, Lisa M.

doi:10.1006/jaut.1999.0343

Cited by 147 publications

(113 citation statements)

References 84 publications

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“…Skin shave biopsies were obtained from two psoriasis patients, and dermal cells allowed to emigrate in culture according to a published protocol (18). Shave biopsies are small superficial (split thickness) skin biopsies that give the largest surface area for efficient emigration of DCs.…”

Section: Methodsmentioning

confidence: 99%

Increase in TNF-α and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a)

Lowes

Chamian

Abello

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

433

379

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We find that CD11c ؉ cells with many markers of dendritic cells (DCs) are a major cell type in the skin lesions of psoriasis. These CD11c ؉ cells, which are evident in both epidermis and dermis, are the sites for the expression of two mediators of inflammation, inducible nitric oxide synthase (iNOS) and TNF-␣ in diseased skin. These cells express HLA-DR, CD40, and CD86, lack the Langerin and CD14 markers of Langerhans cells and monocytes, respectively, and to a significant extent express the DC maturation markers DC-LAMP and CD83. Treatment of psoriasis with efalizumab (antiCD11a, Raptiva) strongly reduces infiltration by these DCs in patients responding to this agent. Disease activity after therapy was more related to DC infiltrates and iNOS mRNA levels than T cell infiltrates, and CD11c ؉ cells responded more quickly to therapy than epidermal keratinocytes. Our results suggest that a type of DC, which resembles murine ''Tip-DCs'' that can accumulate during infection, has proinflammatory effects in psoriasis through nitric oxide and TNF-␣ production, and can be an important target for suppressive therapies.autoimmune disease ͉ CD11c ͉ Tip-DC

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Section: Methodsmentioning

confidence: 99%

Increase in TNF-α and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a)

Lowes

Chamian

Abello

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

433

379

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“…17 Both of these T-cell subsets have type-1 effector functions and can be classified as T c 1 and T h 1 populations, respectively. 18 TNF and IFN-g, are synthesized by these activated T cells and are key cytokines for activating keratinocytes.…”

Section: Immune Cells In Psoriatic Lesionsmentioning

confidence: 99%

Psoriasis: genetic associations and immune system changes

2006

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Psoriasis is a common inflammatory skin disease characterized by infiltration of inflammatory cells into the epidermis and altered keratinocyte differentiation. Psoriasis is currently thought of as a T-cell mediated 'Type-1' autoimmune disease. Gene expression changes in psoriasis lesions have been well documented, and strongly support an important role for tumor necrosis factor and interferon gamma signal pathways in its pathogenesis. The strongest genetic determinant of psoriasis identified to date lies within the class I region of the multiple histocompatibility locus antigen cluster, although its low penetrance implicates a requirement for other genetic risk factors. Multiple genome-wide linkage and an increasing number of association studies have been carried out, leading to multiple linkage peaks, and the identification of potential low risk variants. A number of these variants lie within genes encoding components of the immune system. However, the functional relationships between predisposing genetic variation is unclear, and presumably involves genetic susceptibility factors affecting both immune cell activation and keratinocyte differentiation. The interaction of environmental trigger factors with genetic effects is also not understood, but provide further evidence for the complex basis of this disease.

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“…However, it is now clear that Th1 and Th0 lymphocytes also express CD30 (20,21), and the distinction between Th1 and Th2 disorders based on CD30 expression is not absolute. For example, CD30 + T cells have been found in lesional skin in psoriasis, a chronic inflammatory disorder of the Th1 subtype (22). The contribution of cells expressing CD30L to the pathogenesis in chronic cutaneous inflammatory diseases such as AD and psoriasis is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Mast cell CD30 ligand is upregulated in cutaneous inflammation and mediates degranulation-independent chemokine secretion

Fischer

Harvima²,

Carvalho³

et al. 2006

J. Clin. Invest.

121

124

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Mast cells are involved in many disorders where the triggering mechanism that leads to degranulation and/or cytokine secretion has not been defined. Several chronic inflammatory diseases are associated with increased mast cell numbers and upregulation of the TNF receptor family member CD30, but the role of elevated CD30 expression is poorly understood. Here we report what we believe to be a novel way to activate mast cells with CD30 that leads to degranulation-independent secretion of chemokines. CD30 induced a de novo synthesis and secretion of the chemokines IL-8, macrophage inflammatory protein-1α (MIP-1α), and MIP-1β, a process involving the MAPK/ERK pathway. Mast cells were found to be the predominant CD30 ligand-positive (CD30L-positive) cell in the chronic inflammatory skin diseases psoriasis and atopic dermatitis, and both CD30 and CD30L expression were upregulated in lesional skin in these conditions. Furthermore, the number of IL-8-positive mast cells was elevated both in psoriatic and atopic dermatitis lesional skin as well as in ex vivo CD30-treated healthy skin organ cultures. In summary, characterization of CD30 activation of mast cells has uncovered an IgE-independent pathway that is of importance in understanding the entirety of the role of mast cells in diseases associated with mast cells and CD30 expression. These diseases include Hodgkin lymphoma, atopic dermatitis, and psoriasis.

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CD69, HLA-DR and the IL-2R Identify Persistently Activated T Cells in Psoriasis Vulgaris Lesional Skin: Blood and Skin Comparisons by Flow Cytometry

Cited by 147 publications

References 84 publications

Increase in TNF-α and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a)

Increase in TNF-α and inducible nitric oxide synthase-expressing dendritic cells in psoriasis and reduction with efalizumab (anti-CD11a)

Psoriasis: genetic associations and immune system changes

Mast cell CD30 ligand is upregulated in cutaneous inflammation and mediates degranulation-independent chemokine secretion

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