MRC Human Immunology Unit, NIHR Biomedical Research Centre, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
Department of Plastic and Reconstructive Surgery, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, UK.
Sci Immunol. 2021 May 21;6(59). doi: 10.1126/sciimmunol.abe5084.
Cutaneous group 2 innate lymphoid cells (ILC2) are spatially and epigenetically poised to respond to barrier compromise and associated immunological threats. ILC2, lacking rearranged antigen-specific receptors, are primarily activated by damage-associated cytokines and respond with type 2 cytokine production. To investigate ILC2 potential for direct sensing of skin pathogens and allergens, we performed RNA sequencing of ILC2 derived from in vivo challenged human skin or blood. We detected expression of and by skin and blood ILC2. Stimulation of ILC2 with TLR2 agonist alone not only induced interleukin-5 (IL-5) and IL-13 expression but also elicited IL-6 expression in combination with muramyl dipeptide (MDP). Heat-killed skin-resident bacteria provoked an IL-6 profile in ILC2 in vitro that was notably impaired in ILC2 derived from patients with mutations. In addition, we show that signaling can stimulate autophagy in ILC2, which was also impaired in patients with mutations. Here, we have identified a role for ILC2 NOD2 signaling in the differential regulation of ILC2-derived IL-6 and have reported a previously unrecognized pathway of direct ILC2 bacterial sensing.
皮肤 2 型固有淋巴细胞（ILC2）在空间和表观遗传上都能对屏障损伤和相关免疫威胁做出反应。ILC2 缺乏重排的抗原特异性受体，主要通过损伤相关细胞因子激活，并产生 2 型细胞因子。为了研究 ILC2 对皮肤病原体和过敏原的直接感知潜力，我们对来自体内受挑战的人类皮肤或血液的 ILC2 进行了 RNA 测序。我们检测到皮肤和血液 ILC2 表达 和 。TLR2 激动剂单独刺激 ILC2，不仅诱导白细胞介素 5（IL-5）和白细胞介素 13（IL-13）的表达，而且与 二肽（MDP）联合诱导 IL-6 的表达。热灭活的皮肤常驻细菌在体外引起 ILC2 中 IL-6 谱的变化，而在 突变患者的 ILC2 中明显受损。此外，我们表明 信号可以刺激 ILC2 中的自噬，而在 突变患者中也受损。在这里，我们确定了 ILC2 NOD2 信号在 ILC2 衍生的 IL-6 的差异调节中的作用，并报道了一种以前未被识别的直接 ILC2 细菌感应途径。
