Baran Wojciech, Oehrl Stephanie, Ahmad Fareed, Döbel Thomas, Alt Christina, Buske-Kirschbaum Angelika, Schmitz Marc, Schäkel Knut
Department of Dermatology, Venerology and Allergology, Wroclaw Medical University, Wroclaw, Poland.
Department of Dermatology, Medical Faculty, University of Heidelberg, Heidelberg, Germany.
Front Immunol. 2018 Jun 21;9:1352. doi: 10.3389/fimmu.2018.01352. eCollection 2018.
Mononuclear phagocytes (MPs) are important immune regulatory cells in atopic dermatitis (AD). We previously identified 6-sulfo LacNAc-expressing monocytes (slanMo) as TNF-α- and IL-23-producing cells in psoriatic skin lesions and as inducers of IFN-γ-, IL-17-, and IL-22-producing T cells. These cytokines are also upregulated in AD and normalize with treatment, as recently shown for dupilumab-treated patients. We here asked for the role of slanMo in AD. Increased numbers of slanMo were found in AD skin lesions. In difference to other MPs in AD, slanMo lacked expression of FcɛRI, CD1a, CD14, and CD163. slanMo from blood of patients with AD expressed increased levels of CD86 and produced IL-12 and TNF-α at higher amounts than CD14 monocytes and myeloid dendritic cells. While CD14 monocytes from patients with AD revealed a reduced IL-12 production, we observed no difference in the cytokine production comparing slanMo in AD and healthy controls. Interestingly, experimentally induced mental stress, a common trigger of flares in patients with AD, rapidly mobilized slanMo which retained their high TNF-α-producing capacity. This study identifies slanMo as a distinct population of inflammatory cells in skin lesions and as proinflammatory blood cells in patients with AD. slanMo may, therefore, represent a potent future target for treatment of AD.
单核吞噬细胞（MPs）是特应性皮炎（AD）中重要的免疫调节细胞。我们之前在银屑病皮损中鉴定出表达6-磺基乳糖胺的单核细胞（slanMo）是产生肿瘤坏死因子-α（TNF-α）和白细胞介素-23（IL-23）的细胞，也是诱导产生干扰素-γ（IFN-γ）、白细胞介素-17（IL-17）和白细胞介素-22（IL-22）的T细胞。这些细胞因子在AD中也上调，并在治疗后恢复正常，最近在接受度普利尤单抗治疗的患者中得到证实。我们在此研究了slanMo在AD中的作用。在AD皮损中发现slanMo数量增加。与AD中的其他MPs不同，slanMo缺乏FcɛRI、CD1a、CD14和CD163的表达。来自AD患者血液的slanMo表达的CD86水平升高，产生的IL-12和TNF-α比CD14单核细胞和髓样树突状细胞更多。虽然AD患者的CD14单核细胞显示IL-12产生减少，但我们观察到AD患者的slanMo与健康对照相比，细胞因子产生没有差异。有趣的是，实验诱导的精神压力是AD患者皮疹发作的常见诱因，可迅速动员slanMo，其仍保留高TNF-α产生能力。本研究将slanMo鉴定为皮损中独特的炎症细胞群以及AD患者的促炎血细胞。因此，slanMo可能是未来治疗AD的有效靶点。
