Wenzel Joerg, Henze Stephanie, Wörenkämper Eva, Basner-Tschakarjan Etiena, Sokolowska-Wojdylo Malgorzata, Steitz Julia, Bieber Thomas, Tüting Thomas
Department of Dermatology, University of Bonn, Bonn, Germany.
J Invest Dermatol. 2005 Jun;124(6):1241-8. doi: 10.1111/j.0022-202X.2005.23755.x.
Skin-infiltrating T lymphocytes are thought to play a major role in the pathogenesis of cutaneous lupus erythematosus (CLE). In this study, we investigated the role of the chemokine receptor 4 (CCR4) and its ligand thymus- and activation-regulated chemokine (TARC/CCL17) for the recruitment of T cells in inflamed skin of patients with CLE. We found significant numbers of CCR4+ T lymphocytes in the skin of all patients with CLE. Interestingly, a subset of patients with disseminated scarring skin involvement were characterized by both lesional and circulating CD8+ T cells expressing CCR4. Destruction of epidermal and adnexal structures was histomorphologically associated with CCR4+ cytotoxic T cells invading basal layers of the epidermis where keratinocytes showed apoptotic death. The CCR4 ligand TARC/CCL17 was strongly expressed in skin lesions and elevated in the serum of CLE patients. The functional relevance of lymphocytic CCR4 expression could be confirmed by TARC/CCL17-specific in vitro migration assays. Our investigations suggest that CCR4 and TARC/CCL17 play a role in the pathophysiology of CLE. In particular, cytotoxic CD8+ T cells expressing CCR4 appear to be involved in scarring subtypes of CLE.
皮肤浸润性T淋巴细胞被认为在皮肤红斑狼疮（CLE）的发病机制中起主要作用。在本研究中，我们调查了趋化因子受体4（CCR4）及其配体胸腺和活化调节趋化因子（TARC/CCL17）在CLE患者炎症皮肤中T细胞募集方面的作用。我们在所有CLE患者的皮肤中发现了大量CCR4+ T淋巴细胞。有趣的是，一部分有弥漫性瘢痕性皮肤受累的患者其特征为病变部位和循环中的CD8+ T细胞均表达CCR4。表皮和附属器结构的破坏在组织形态学上与CCR4+ 细胞毒性T细胞侵入表皮基底层有关，在该部位角质形成细胞出现凋亡性死亡。CCR4配体TARC/CCL17在皮肤病变中强烈表达，且在CLE患者血清中升高。淋巴细胞CCR4表达的功能相关性可通过TARC/CCL17特异性体外迁移试验得到证实。我们的研究表明，CCR4和TARC/CCL17在CLE的病理生理学中起作用。特别是，表达CCR4的细胞毒性CD8+ T细胞似乎参与了CLE的瘢痕形成亚型。
