固有淋巴细胞亚群在人类皮肤中的组成:银屑病患者皮损和血液中 NCR(+) ILC3 的富集。
Composition of innate lymphoid cell subsets in the human skin: enrichment of NCR(+) ILC3 in lesional skin and blood of psoriasis patients.
机构信息
Department of Dermatology, University of Amsterdam, Amsterdam, The Netherlands.
Department of Hematology, University of Amsterdam, Amsterdam, The Netherlands.
出版信息
J Invest Dermatol. 2014 Sep;134(9):2351-2360. doi: 10.1038/jid.2014.146. Epub 2014 Mar 21.
Innate lymphoid cells (ILCs) are increasingly appreciated as important regulators of tissue homeostasis and inflammation. However, their role in human skin remains obscure. We found that healthy peripheral blood CD117(+) ILC3, lacking the natural cytotoxicity receptor (NCR) NKp44 (NCR(-) ILC3), CD117(-)NCR(-)CRTH2(-)CD161(+) ILC1, and CRTH2(+) ILC2, express the skin-homing receptor cutaneous lymphocyte antigen (CLA). NCR(+) ILC3 were scarce in peripheral blood. Consistently, we identified in normal skin ILC2 and NCR(-) ILC3, a small proportion of CD161(+) ILC1, and hardly any NCR(+) ILC3, whereas NCR(+) ILC3 were present in cultured dermal explants. The skin ILC2 and NCR(+) ILC3 subsets produced IL-13 and IL-22, respectively, upon cytokine stimulation. Remarkably, dermal NCR(-) ILC3 converted to NCR(+) ILC3 upon culture in IL-1β plus IL-23, cytokines known to be involved in psoriatic inflammation. In line with this observation, significantly increased proportions of NCR(+) ILC3 were present in lesional skin and peripheral blood of psoriasis patients as compared with skin and blood of healthy individuals, respectively, whereas the proportions of ILC2 and CD161(+) ILC1 remained unchanged. NCR(+) ILC3 from skin and blood of psoriasis patients produced IL-22, which is regarded as a key driver of epidermal thickening, suggesting that NCR(+) ILC3 may participate in psoriasis pathology.
固有淋巴细胞 (ILC) 被认为是组织稳态和炎症的重要调节因子。然而,它们在人类皮肤中的作用尚不清楚。我们发现,健康外周血 CD117(+) ILC3,缺乏自然细胞毒性受体 (NCR) NKp44(NCR(-) ILC3)、CD117(-)NCR(-)CRTH2(-)CD161(+) ILC1 和 CRTH2(+) ILC2,表达皮肤归巢受体皮肤淋巴细胞抗原 (CLA)。外周血中 NCR(+) ILC3 较少。一致地,我们在正常皮肤中鉴定出 ILC2 和 NCR(-) ILC3、一小部分 CD161(+) ILC1 和几乎没有 NCR(+) ILC3,而 NCR(+) ILC3 存在于培养的真皮外植体中。皮肤 ILC2 和 NCR(+) ILC3 亚群在细胞因子刺激下分别产生 IL-13 和 IL-22。值得注意的是,真皮 NCR(-) ILC3 在 IL-1β 加 IL-23 的培养下转化为 NCR(+) ILC3,这两种细胞因子已知参与银屑病炎症。与此观察结果一致,与健康个体的皮肤和血液相比,银屑病患者的皮损皮肤和外周血中 NCR(+) ILC3 的比例显著增加,而 ILC2 和 CD161(+) ILC1 的比例保持不变。来自银屑病患者皮肤和血液的 NCR(+) ILC3 产生 IL-22,被认为是表皮增厚的关键驱动因素,这表明 NCR(+) ILC3 可能参与银屑病的发病机制。