Innate immune-related receptors in normal and psoriatic skin.
BACKGROUND
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.


METHODS
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)-kappaB 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.
Curry
Jonathan L
JL
Department of Pathology, Skin Cancer Research Laboratories, Loyola University Cancer Center, Maywood, IL 60153, USA.
Qin
Jian-Zhong
JZ
Bonish
Brian
B
Carrick
Ryan
R
Bacon
Patricia
P
Panella
Jeffrey
J
Robinson
June
J
Nickoloff
Brian J
BJ
D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology; D003713:Dendritic Cells / Q000737:chemistry / Q000166:cytology / Q000276:immunology / Q000473:pathology; D020405:Dermis / Q000737:chemistry / Q000166:cytology / Q000473:pathology; D029721:Drosophila Proteins; D000078404:Epidermal Cells; D004817:Epidermis / Q000737:chemistry / Q000473:pathology; D005347:Fibroblasts / Q000737:chemistry / Q000166:cytology / Q000473:pathology / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000737:chemistry / Q000166:cytology / Q000473:pathology / Q000502:physiology; D026502:LDL-Receptor Related Proteins / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000276:immunology; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000502:physiology; D016328:NF-kappa B / Q000096:biosynthesis / Q000502:physiology; D011565:Psoriasis / Q000276:immunology* / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology / Q000502:physiology; D012867:Skin / Q000166:cytology / Q000378:metabolism*; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors
D018834:Chaperonin 60; D029721:Drosophila Proteins; D018840:HSP70 Heat-Shock Proteins; D026502:LDL-Receptor Related Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C495371:TLR9 protein, human; D051194:Toll-Like Receptor 1; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors