Epidermal keratinocytes express the adhesion molecule intercellular adhesion molecule-1 in inflammatory dermatoses

Singer, Kay H.; Tuck, Debbi T.; Sampson, Hugh A.; Hall, Russell P.

doi:10.1016/0022-202x(89)90193-0

Cited by 109 publications

(65 citation statements)

References 42 publications

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“…Infiltrating T cells were predominantly confined to lower and mid-epidermal zones with a variable extent of infiltration amongst different grafts, and T cells displayed a nonrandom migration pattern after intradermal injection that was indistinguishable from idiopathic psoriatic plaques (28). There was also epidermal keratinocyte intercellular adhesion molecule-1 (ICAM-1) expression that accompanied the intra-epidermal T cells (data not shown) as previously described (29,30). In terms of APCs, there were only rare scattered CD1a positive epidermal Langerhans cell in the epidermis, but there were numerous factor XIIIa positive dermal dendritic cells (data not shown).…”

Section: Resultssupporting

confidence: 74%

Dermal injection of immunocytes induces psoriasis.

Wrone-Smith

Nickoloff²

1996

J. Clin. Invest.

408

304

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Establishing direct and causal relationships among the confederacy of activated cell types present in psoriasis has been hampered by lack of an animal model. Within psoriatic plaques there are hyperplastic keratinocytes, infiltrating immunocytes, and activated endothelial cells. The purpose of this study was to determine if psoriasis is primarily a disorder of keratinocytes or the immune system. Using a newly developed experimental system in which full-thickness human skin is orthotopically transferred onto severe combined immunodeficient mice, autologous immunocytes were injected into dermis, and the resultant phenotype characterized by clinical, histologic, and immunophenotypic analyses. Engraftment of samples included both uninvolved/ symptomless (PN) skin removed from patients with psoriasis elsewhere, or from healthy individuals with no skin disease (NN skin). In 10 different experiments involving 6 different psoriasis patients, every PN skin was converted to a full-fledged psoriatic plaque skin by injection of autologous blood-derived immunocytes. In all but one psoriatic patient, the immunocytes required preactivation with IL-2 and superantigens to convert PN skin into psoriatic plaque skin. In every case, resultant plaques were characterized by visible presence of flaking and thickened skin, loss of the granular cell layer, prominent elongation of rete pegs with a dermal angiogenic tissue reaction, and infiltration within the epidermis by T cells. Lesional skin displayed 20 different antigenic determinants of the psoriatic phenotype. None of the four NN skin samples injected with autologous immunocytes converted to psoriatic plaques. We conclude that psoriasis is caused primarily by the ability of pathogenetic blood-derived immunocytes to induce secondary activation and disordered growth of endogenous cutaneous cells including keratinocytes and vascular endothelium. ( J. Clin. Invest. 1996. 98:1878-1887.)

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Section: Resultssupporting

confidence: 74%

Dermal injection of immunocytes induces psoriasis.

Wrone-Smith

Nickoloff²

1996

J. Clin. Invest.

408

304

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“…Accordingly, a reduced chemokine stimulus for cell migration into skin seems more likely as a mechanism to explain decreased migration of leukocytes into the dermis. In contrast, ICAM-1 expression by keratinocytes is down-regulated during etanercept treatment; thus, migration of leukocytes from the dermis into the epidermis could be blocked by direct modulation of adhesion molecules (60,61).…”

Section: Discussionmentioning

confidence: 99%

TNF Inhibition Rapidly Down-Regulates Multiple Proinflammatory Pathways in Psoriasis Plaques

Gottlieb¹,

Chamian

Masud³

et al. 2005

The Journal of Immunology

344

264

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The mechanisms of action of marketed TNF-blocking drugs in lesional tissues are still incompletely understood. Because psoriasis plaques are accessible to repeat biopsy, the effect of TNF/lymphotoxin blockade with etanercept (soluble TNFR) was studied in ten psoriasis patients treated for 6 months. Histological response, inflammatory gene expression, and cellular infiltration in psoriasis plaques were evaluated. There was a rapid and complete reduction of IL-1 and IL-8 (immediate/early genes), followed by progressive reductions in many other inflammation-related genes, and finally somewhat slower reductions in infiltrating myeloid cells (CD11c+ cells) and T lymphocytes. The observed decreases in IL-8, IFN-γ-inducible protein-10 (CXCL10), and MIP-3α (CCL20) mRNA expression may account for decreased infiltration of neutrophils, T cells, and dendritic cells (DCs), respectively. DCs may be less activated with therapy, as suggested by decreased IL-23 mRNA and inducible NO synthase mRNA and protein. Decreases in T cell-inflammatory gene expression (IFN-γ, STAT-1, granzyme B) and T cell numbers may be due to a reduction in DC-mediated T cell activation. Thus, etanercept-induced TNF/lymphotoxin blockade may break the potentially self-sustaining cycle of DC activation and maturation, subsequent T cell activation, and cytokine, growth factor, and chemokine production by multiple cell types including lymphocytes, neutrophils, DCs, and keratinocytes. This results in reversal of the epidermal hyperplasia and cutaneous inflammation characteristic of psoriatic plaques.

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“…Eczematous skin lesions with distinct etiology are associated with T-cell infiltration in the epidermis, contact between T cells and KCs, and a marked KC pathology (28,50,51). KCs in inflamed skin express HLA-DR and ICAM-1, which are not expressed on KCs of normal skin (1,2). The only mediator known to date that induces HLA-DR on KCs is IFN-γ.…”

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confidence: 99%