Composition of Innate Lymphoid Cell Subsets in the Human Skin: Enrichment of NCR+ ILC3 in Lesional Skin and Blood of Psoriasis Patients
Composition of Innate Lymphoid Cell Subsets in the Human Skin: Enrichment of NCR+ ILC3 in Lesional Skin and Blood of Psoriasis Patients
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DOI：
10.1038/jid.2014.146
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发表时间：
2014-09-01
影响因子：
6.5
通讯作者：
Mjosberg, Jenny
中科院分区：
文献类型：
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作者：
Teunissen, Marcel B. M.;Munneke, J. Marius;Mjosberg, Jenny
先天性淋巴样细胞（ILC）作为组织稳态和炎症的重要调节因子越来越受到重视。然而，它们在人类皮肤中的作用仍然不清楚。我们发现，缺乏天然细胞毒性受体（NCR）NKp 44（NCR-ILC 3）的健康外周血CD 117（+）ILC 3、CD 117（-）NCR（-）CRTH 2（-）CD 161（+）ILC 1和CRTH 2（+）ILC 2表达皮肤归巢受体皮肤淋巴细胞抗原（CLA）。NCR+ ILC 3在外周血中缺乏。一致地，我们在正常皮肤ILC 2和NCR-ILC 3中鉴定了小比例的CD 161（+）ILC 1，并且几乎没有任何NCR+ ILC 3，而NCR+ ILC 3存在于培养的真皮外植体中。皮肤ILC 2和NCR+ ILC 3亚群在细胞因子刺激后分别产生IL-13和IL-22。值得注意的是，在IL-1 β加IL-23（已知参与银屑病炎症的细胞因子）中培养时，真皮NCR-ILC 3转化为NCR+ ILC 3。与该观察结果一致，分别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+ ILC 3的比例显著增加，而ILC 2和CD 161（+）ILC 1的比例保持不变。来自银屑病患者皮肤和血液的NCR+ ILC 3产生IL-22，其被认为是表皮增厚的关键驱动因素，表明NCR+ ILC 3可能参与银屑病病理。
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-1 beta 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.