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皮肤红斑狼疮中的树突状细胞:病变发病机制的线索

Dendritic cells in cutaneous lupus erythematosus: a clue to the pathogenesis of lesions.

作者信息

Mori M, Pimpinelli N, Romagnoli P, Bernacchi E, Fabbri P, Giannotti B

机构信息

II Dermatology Clinic, University of Florence, Italy.

出版信息

Histopathology. 1994 Apr;24(4):311-21. doi: 10.1111/j.1365-2559.1994.tb00531.x.

DOI:10.1111/j.1365-2559.1994.tb00531.x
PMID:8045520
Abstract

In view of the critical role of dendritic cells in immune mediated skin diseases, we have investigated the membrane antigen patterns and ultrastructure of cutaneous dendritic cells in eight patients with chronic discoid lupus erythematosus and five with subacute cutaneous lupus erythematosus. In the lesional epidermis, the expression of HLA-DR antigens by epidermal dendritic cells was reduced, as compared with perilesional, clinically normal skin. In addition, only few CD1a+ dendritic cells (Langerhans' cells), along with some CD11c+ and CD14+ cells (presumable precursors of Langerhans' cells), were found in atrophic areas of lesional epidermis. In contrast, the number of Langerhans' cells in non-atrophic areas of lesional epidermis was similar to that in perilesional skin. On electronmicroscopy, epidermal Langerhans' cells appeared depleted of organelles and dendrites and contained tubuloreticular inclusions. In the lesional dermis, both CD1a+ and CD36+ dendritic cells were found, associated with CD4+ and CD8+ T-cells, respectively. Moreover, CD11c+ and CD14+ cells were found around capillaries in the papillary dermis on electronmicroscopy. Indeterminate cells (dendritic cells with features of Langerhans' cell lineage, but apparently without Birbeck granules) and dendritic macrophages were found, associated with lymphocytes and mast cells. No cells with intermediate/transitional features between these two dendritic cell types were found. Conversely, peculiar dendritic cells--with short and blunt dendrites and cytoplasm containing many flat, rough cisternae, moderately well developed Golgi apparatus and no lysosomes--were found in the same location as the CD11c+ and CD14+ cells identified by light microscopy. These findings might be interpreted as follows: 1 the alterations in cytological differentiation and expression of functionally meaningful molecules by epidermal Langerhans' cells in cutaneous lupus erythematosus lesions suggest an impairment of their immunological efficiency; 2 in the lesional dermis of cutaneous lupus erythematosus, a CD4+ T-cell/CD1a+ dendritic cell-based, delayed-type immune response is possibly modulated by a suppressor T-cell circuit in which CD36+ dendritic cells may act as accessory cells; 3 CD11c+ and CD14+ cells with peculiar ultrastructure are possible precursors of both CD1a+ indeterminate cells and CD36+ dermal dendrocytes in the dermis.

摘要

鉴于树突状细胞在免疫介导的皮肤疾病中起关键作用,我们研究了8例慢性盘状红斑狼疮患者和5例亚急性皮肤型红斑狼疮患者皮肤树突状细胞的膜抗原模式和超微结构。在皮损表皮中,与皮损周围临床正常皮肤相比,表皮树突状细胞HLA-DR抗原的表达减少。此外,在皮损表皮的萎缩区域仅发现少数CD1a+树突状细胞(朗格汉斯细胞),以及一些CD11c+和CD14+细胞(可能是朗格汉斯细胞的前体)。相反,皮损表皮非萎缩区域的朗格汉斯细胞数量与皮损周围皮肤相似。电镜下,表皮朗格汉斯细胞细胞器和树突减少,含有管状嵴包涵体。在皮损真皮中,发现了CD1a+和CD36+树突状细胞,分别与CD4+和CD8+ T细胞相关。此外,电镜下在乳头真皮的毛细血管周围发现了CD11c+和CD14+细胞。发现了不确定细胞(具有朗格汉斯细胞系特征但显然没有伯贝克颗粒的树突状细胞)和树突状巨噬细胞,它们与淋巴细胞和肥大细胞相关。未发现这两种树突状细胞类型之间具有中间/过渡特征的细胞。相反,在光镜下鉴定出的CD11c+和CD14+细胞所在位置发现了特殊的树突状细胞——具有短而钝的树突,细胞质中含有许多扁平的粗面内质网,高尔基体中度发育良好且无溶酶体。这些发现可能如下解释:1. 皮肤红斑狼疮皮损中表皮朗格汉斯细胞的细胞学分化和功能有意义分子表达的改变提示其免疫效率受损;2. 在皮肤红斑狼疮的皮损真皮中,基于CD4+ T细胞/CD1a+树突状细胞的迟发型免疫反应可能受抑制性T细胞回路调节,其中CD36+树突状细胞可能作为辅助细胞;3. 具有特殊超微结构的CD11c+和CD14+细胞可能是真皮中CD1a+不确定细胞和CD36+真皮树突状细胞的前体。

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