Innate Immune-Related Receptors in Normal and Psoriatic Skin

Abstract

Context.—A precise role for the innate immune system in psoriasis remains to be determined. Surface receptors, including Toll-like receptors (TLRs) that recognize bacterial ligands and CD91, which recognizes heat shock proteins (HSPs), are implicated in both innate and adaptive immunity. Objective.—Since skin is exposed to various exogenous stimuli, which can provoke or exacerbate psoriasis, we characterized expression and function of TLRs, CD91, and HSPs in normal and psoriatic skin. Design.—A variety of skin-derived cells and blood-derived cells were analyzed both in vivo and in vitro; samples were obtained from 24 different individuals for innate immune-related receptor expression and function. By comparing and contrasting individuals with healthy skin and psoriatic patients, several specific differences were identified. Results.—Immunohistochemistry-based expression profiling revealed TLR1 expression in epidermal dendritic cells (DCs) and dermal dendritic cells (DDCs) in normal skin, as well as in pre-psoriatic skin and psoriatic plaques, with enhanced basal layer keratinocyte (KC) expression in pre-psoriatic and psoriatic plaques compared with normal skin; TLR2 expression primarily by DDCs; and TLR4 expression by epidermal DCs and DDCs, with mid-epidermal-layer KCs displaying cell surface staining. No TLR9 or CD14 was detected on DCs or KCs, although psoriatic plaques contained CD14-positive macrophages. Analysis of psoriatic epidermis revealed HSPs 27, 60, and 70. Keratinocytes were CD91 negative, but CD91 was expressed by fibroblasts and DDCs in normal and pre-psoriatic skin, with prominent accumulation of CD91-positive DDCs in psoriatic plaques. Cultured KCs revealed no surface expression of TLR2, TLR4, TLR9, or CD91. Exposure of fibroblasts, but not KCs, to lipopolysaccharide or HSPs triggered nuclear factor (NF)-κB activation. Heat shock proteins did induce maturation of blood-derived DCs accompanied by increased interleukin-12 production and enhanced antigen-presenting function. Conclusions.—These data demonstrate distinctive patterns of innate immune-related receptors by specific subsets of cells in normal and psoriatic skin, suggesting functional roles for HSPs and DCs in psoriasis.

Psoriasis Triggered by Toll-like Receptor 7 Agonist Imiquimod in the Presence of Dermal Plasmacytoid Dendritic Cell Precursors

“…32,33 In recent years, the observation that psoriatic plaques are resistant to microbial infection despite a compromised skin barrier has led to growing interest in functions of the innate immune system in psoriatic skin. [34][35][36] A role for innate immune responses as a trigger of the pathogenic T-cell cascade leading to psoriasis has been suggested; however, there is no direct evidence. Murine models have demonstrated that TLR activation may provide signals to elicit T-cellmediated autoimmunity.…”

IFN-α Enhances Poly-IC Responses in Human Keratinocytes by Inducing Expression of Cytosolic Innate RNA Receptors: Relevance for Psoriasis

“…Clinical relevance of this finding is illustrated by the observation that expression of these receptors is significantly increased in psoriasis lesional skin. Although the expression of family members of the TLR family was studied extensively in human KCs and psoriatic skin (Song et al, 2002;Baker et al, 2003;Curry et al, 2003;Mempel et al, 2003;Pivarcsi et al, 2003;Kollisch et al, 2005;Lebre et al, 2007), minimal data are available on the expression of the RNA helicases RIG-I and MDA5 in KCs and inflamed skin.…”

“…Keratinocytes (KCs), the major cell type present in the epidermis, can exert many immunological functions such as cytokine and chemokine production, cell adhesion, and antigen presentation, and can therefore be regarded as immunecompetent cells. KCs are responsive to stimulation with various PAMPs, and TLR expression on human KCs has been studied extensively (Song et al, 2002;Baker et al, 2003;Curry et al, 2003;Mempel et al, 2003;Pivarcsi et al, 2003;Kollisch et al, 2005;Tohyama et al, 2005;Lebre et al, 2007). In contrast, very little is known about KCs expression of members of the other families of pattern recognition receptor families such as the NOD-like receptors or the RIGlike helicases.…”

Presencia de receptores tipo Toll (TLR2 y TLR4) en actinomicetomas por <i>Actinomadura madurae</i>

“…13 El complejo CD14-TLR4/4MD-2 se une al lipopolisacárido (LPS) de bacterias Gram-negativas, a la proteína F viral (induce la secreción de proteínas de choque térmico), 14,15 el TLR5 se une a la flagelina bacteriana, 16,17 y el TLR9 que se encuentra en el retículo endoplásmico participa en la iniciación de la respuesta inmune, seguida al daño epidérmico o infección. [18][19][20] El objetivo de este trabajo es demostrar la presencia in situ de los receptores TLR2 y TLR4, en queratinocitos de piel, en cortes de pacientes con actinomicetoma por Actinomadura madurae, mediante el uso de técnicas inmunohistoquímicas.…”