Faculty of Medicine, Institute of Immunology, Technical University of Dresden, Dresden, Germany.
J Allergy Clin Immunol. 2011 Mar;127(3):787-94.e1-9. doi: 10.1016/j.jaci.2010.12.009.
Psoriasis is a chronic inflammatory skin disease that is considered to result from activated T cells stimulated by a population of inflammatory dermal dendritic cells (DCs). The origin and identity of these inflammatory dermal DCs are largely unknown.
We previously identified slanDCs (6-sulfo LacNAc) DCs as a rich source of TNF-α and as the early major source of IL-12. Here we studied the relevance of slanDCs as inflammatory dermal DCs in psoriasis.
Psoriasis skin samples were stained for the presence of activated slanDCs. Functional studies were carried out to determine the cytokine production of slanDCs, their T(h)17/T(h)1 T-cell programming, and their migration behavior.
Large numbers of IL-23, TNF-α, and inducible nitric oxide synthase expressing slanDCs were found in psoriatic skin samples, which can be recruited by C5a, CX3CL1, and CXCL12. SlanDCs isolated from blood produced high levels of IL-1ß, IL-23, IL-12, and IL-6. Compared with classic CD1c(+) DCs, slanDCs were far more powerful in programming T(h)17/T(h)1 T cells that secrete IL-17, IL-22, TNF-α, and IFN-γ, yet CD1c(+) DCs induced a higher IL-10 production of T cells. Self-nucleic acids complexed to cathelicidin LL37 trigger endosomal Toll-like receptor (TLR) signaling (TLR7, TLR8, TLR9) and are key factors for the activation of DCs in psoriasis. We show that slanDCs respond particularly well to complexes formed of self-RNA and LL37. Similarly, slanDCs stimulated with a synthetic TLR7/8 ligand produced high levels of proinflammatory cytokines.
Our study defines slanDCs as inflammatory dermal DCs in psoriasis and identifies their strong capacity to induce T(h)17/T(h)1 responses.
银屑病是一种慢性炎症性皮肤病，被认为是由被炎症性真皮树突状细胞 (DC) 刺激的活化 T 细胞引起的。这些炎症性真皮 DC 的起源和身份在很大程度上是未知的。
我们之前发现 slanDCs（6-硫酸乳糖酰神经氨酸）DC 是 TNF-α 的丰富来源，也是 IL-12 的早期主要来源。在这里，我们研究了 slanDCs 作为银屑病中炎症性真皮 DC 的相关性。
对银屑病皮肤样本进行活化 slanDCs 的存在染色。进行功能研究以确定 slanDCs 的细胞因子产生、其 T(h)17/T(h)1 T 细胞编程和迁移行为。
在银屑病皮肤样本中发现大量表达 IL-23、TNF-α 和诱导型一氧化氮合酶的 slanDCs，这些细胞可以被 C5a、CX3CL1 和 CXCL12 募集。从血液中分离的 slanDCs 产生高水平的 IL-1ß、IL-23、IL-12 和 IL-6。与经典的 CD1c(+) DC 相比，s lanDCs 在编程分泌 IL-17、IL-22、TNF-α 和 IFN-γ 的 T(h)17/T(h)1 T 细胞方面更强大，而 CD1c(+) DC 诱导 T 细胞产生更高水平的 IL-10。与抗菌肽 LL37 复合的自身核酸触发内体 Toll 样受体 (TLR) 信号 (TLR7、TLR8、TLR9)，是银屑病中 DC 活化的关键因素。我们表明 slanDCs 对自身 RNA 和 LL37 形成的复合物特别敏感。同样，用合成 TLR7/8 配体刺激的 slanDCs 产生高水平的促炎细胞因子。
我们的研究将 slanDCs 定义为银屑病中的炎症性真皮 DC，并确定其诱导 T(h)17/T(h)1 反应的强大能力。
