Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Department of Clinical Microbiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
Clin Exp Immunol. 2021 Feb;203(2):230-243. doi: 10.1111/cei.13540. Epub 2020 Nov 17.
Galectin-10 is involved in the T cell suppressive activity of regulatory T cells and eosinophils alike. We have identified a subpopulation of T cell suppressive eosinophils that express CD16 on the surface and contain more galectin-10 compared with conventional CD16-negative eosinophils. Our main goal was to determine how the intracellular protein galectin-10 is released from eosinophils when exposed to proliferating T cells and if such release could be inhibited. Confocal microscopy and imaging flow cytometry were used to study the release of galectin-10 from eosinophils incubated with polyclonally activated T cells. T cell proliferation was monitored by measurement of the incorporation of [ H]-thymidine. Initially, galectin-10-containing synapses formed between eosinophils and T cells. Subsequently, the plasma membrane of eosinophils began to disintegrate and cap-like accumulations of galectin-10 budded on the eosinophil cell surface. Lastly, eosinophil extracellular traps composed of nuclear DNA and galectin-10 were freed. It was solely the CD16-expressing suppressive eosinophils that formed synapses and eosinophil extracellular traps containing galectin-10. Dissolution of the extracellular traps by DNase I partly abrogated the T cell suppression exerted by eosinophils. Extracellular trap formation has mainly been associated with anti-bacterial defense, but we show a new putative function of these cellular formations, as mediators of T cell suppression by enabling the release of galectin-10 from eosinophils.
半乳糖凝集素-10 参与调节性 T 细胞和嗜酸性粒细胞的 T 细胞抑制活性。我们已经鉴定出一种表达表面 CD16 的 T 细胞抑制性嗜酸性粒细胞亚群,与传统的 CD16 阴性嗜酸性粒细胞相比,其含有更多的半乳糖凝集素-10。我们的主要目标是确定当暴露于增殖的 T 细胞时,细胞内蛋白半乳糖凝集素-10 如何从嗜酸性粒细胞中释放出来,以及这种释放是否可以被抑制。共聚焦显微镜和成像流式细胞术用于研究与多克隆激活的 T 细胞孵育的嗜酸性粒细胞中半乳糖凝集素-10 的释放。通过测量 [ H]-胸苷的掺入来监测 T 细胞的增殖。最初,嗜酸性粒细胞和 T 细胞之间形成了含有半乳糖凝集素-10 的突触。随后,嗜酸性粒细胞的质膜开始解体,半乳糖凝集素-10 的帽状聚集物在嗜酸性粒细胞表面发芽。最后,由核 DNA 和半乳糖凝集素-10 组成的嗜酸性粒细胞细胞外陷阱被释放。只有表达 CD16 的抑制性嗜酸性粒细胞形成突触和含有半乳糖凝集素-10 的嗜酸性粒细胞细胞外陷阱。DNase I 溶解细胞外陷阱部分消除了嗜酸性粒细胞对 T 细胞的抑制作用。细胞外陷阱的形成主要与抗细菌防御有关,但我们展示了这些细胞形成物的一个新的潜在功能,即通过允许半乳糖凝集素-10 从嗜酸性粒细胞中释放,作为 T 细胞抑制的介质。