Baker B S, Ovigne J-M, Powles A V, Corcoran S, Fry L
Department of Dermatology, Faculty of Medicine, Imperial College of Science, Technology and Medicine, St Mary's Campus, Norfolk Place, Paddington, London W2 1PG, UK.
Br J Dermatol. 2003 Apr;148(4):670-9. doi: 10.1046/j.1365-2133.2003.05287.x.
Toll-like receptors (TLRs) are part of the innate immune system involved in the response to microbial pathogens. TLR2 recognizes various ligands expressed by Gram-positive bacteria, while TLR3, TLR4 and TLR5 are specific for double-stranded RNA, Gram-negative lipopolysaccharides and bacterial flagellin, respectively.
To determine, firstly, whether epidermal keratinocytes of normal skin express TLRs and, secondly, whether modulation of TLR expression occurs in psoriasis, an inflammatory skin disease associated with certain microorganisms such as streptococci, staphylococci and yeasts.
Eight samples of normal, and 15 samples of lesional and nonlesional psoriatic skin were stained with polyclonal antibodies specific for TLR1-5 using an avidin-biotin-peroxidase technique.
Epidermal keratinocytes in normal skin constitutively expressed TLR1, TLR2 and TLR5, while TLR3 and TLR4 were, in most cases, barely detectable. Cytoplasmic TLR1 and TLR2 were expressed throughout the epidermis, with higher staining of the latter on basal keratinocytes, while TLR5 expression was concentrated in the basal layer. In contrast, in lesional epidermis from patients with psoriasis, TLR2 was more highly expressed on the keratinocytes of the upper epidermis than on the basal layer, while TLR5 was downregulated in basal keratinocytes compared with corresponding nonlesional psoriatic epidermis. In addition, nuclear TLR1 staining was observed in the upper layers of both nonlesional and lesional psoriatic epidermis, but not in that of normal skin.
These findings suggest that TLRs expressed by epidermal keratinocytes constitute part of the innate immune system of the skin. The relevance of altered keratinocyte TLR expression in psoriasis remains to be determined.
Toll样受体（TLRs）是先天性免疫系统的一部分，参与对微生物病原体的应答。TLR2识别革兰氏阳性菌表达的各种配体，而TLR3、TLR4和TLR5分别对双链RNA、革兰氏阴性菌脂多糖和细菌鞭毛蛋白具有特异性。
首先确定正常皮肤的表皮角质形成细胞是否表达TLRs，其次确定在银屑病（一种与某些微生物如链球菌、葡萄球菌和酵母菌相关的炎症性皮肤病）中TLR表达是否发生调节。
使用抗生物素蛋白-生物素-过氧化物酶技术，用针对TLR1-5的多克隆抗体对8份正常皮肤样本以及15份银屑病皮损和非皮损皮肤样本进行染色。
正常皮肤的表皮角质形成细胞组成性表达TLR1、TLR2和TLR5，而在大多数情况下，TLR3和TLR4几乎检测不到。细胞质TLR1和TLR2在整个表皮均有表达，后者在基底角质形成细胞上染色更强，而TLR5表达集中在基底层。相比之下，在银屑病患者的皮损表皮中，TLR2在上层表皮角质形成细胞上的表达高于基底层，而与相应的银屑病非皮损表皮相比，基底角质形成细胞中的TLR5表达下调。此外，在银屑病非皮损和皮损表皮的上层均观察到核TLR1染色，但正常皮肤中未观察到。
这些发现表明，表皮角质形成细胞表达的TLRs构成皮肤先天性免疫系统的一部分。银屑病中角质形成细胞TLR表达改变的相关性仍有待确定。
