BACKGROUND Expansion of type 2 innate lymphoid cells (ILC2s) in hypercholesterolaemic mice protects against atherosclerosis while different ILC2 subsets have been described (natural, inflammatory) based on their suppression of tumorigenicity 2 (ST2) and killer-cell lectin like receptor G1 (KLRG1) expression. The aim of the current study is to characterize the interleukin 25 (IL25)-induced splenic ILC2 population (Lin-CD45+IL17RB+ICOS+IL7raintermediate) and address its direct role in experimental atherosclerosis by its adoptive transfer to hypercholesterolaemic apolipoprotein E deficient (apoE-/-) mice. RESULTS Immunomagnetically enriched, FACS-sorted ILC2s from the spleens of IL-25 treated apoE-/- mice were stained for KLRG1 and ST2 directly upon cell obtainment or in vitro cell expansion for flow cytometric analysis. IL25-induced splenic ILC2s express high levels of both KLRG1 and ST2. However, both markers are downregulated upon in vitro cell expansion. In vitro expanded splenic ILC2s were intraperitoneally transferred to apoE-/- recipients on high fat diet. ApoE-/- mice that received in vitro expanded splenic ILC2s had decreased lipid content in subvalvular heart and brachiocephalic artery (BCA) plaques accompanied by increased peritoneal B1 cells, activated eosinophils and alternatively activated macrophages (AAMs) as well as anti-phosphorylcholine (PC) immunoglobulin (Ig) M in plasma. CONCLUSIONS With the current data we designate the IL25-induced ILC2 population to decrease the lipid content of atherosclerotic lesions in apoE-/- mice and we directly link the induction of B1 cells and the atheroprotective anti-PC IgM antibodies with ILC2s.

中文翻译：

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ILC2转移至载脂蛋白E缺陷型小鼠可降低动脉粥样硬化病变的脂质含量。

背景高胆固醇血症小鼠中2型先天淋巴样细胞（ILC2s）的扩张可预防动脉粥样硬化，而基于其抑制致瘤性2（ST2）和杀伤细胞凝集素样受体G1（KLRG1），已描述了不同的ILC2亚群（天然的，炎性的）。表达。本研究的目的是鉴定白介素25（IL25）诱导的脾ILC2群体（Lin-CD45 + IL17RB + ICOS + IL7raintermediate）并通过将其过继转移至高胆固醇血症性载脂蛋白E缺乏症（apoE）来解决其在实验性动脉粥样硬化中的直接作用。 -/-） 老鼠。结果从获得IL-25的apoE-/-小鼠脾脏中富集了FACS的免疫磁化ILC2，在获得细胞或体外细胞扩增后直接对其进行了KLRG1和ST2染色，以进行流式细胞术分析。IL25诱导的脾ILC2表达高水平的KLRG1和ST2。但是，两种标记在体外细胞扩增后均被下调。在高脂肪饮食下，将体外扩增的脾脏ILC2腹膜内转移至apoE-/-受体。接受体外扩增的脾ILC2s的ApoE-/-小鼠的瓣膜下心脏和臂头动脉（BCA）斑块中的脂质含量降低，并伴有腹膜B1细胞，活化的嗜酸性粒细胞和活化的巨噬细胞（AAM）以及抗磷酸胆碱（PC）的增加）血浆中的免疫球蛋白（Ig）M。结论利用目前的数据，我们指定IL25诱导的ILC2群体减少apoE-/-小鼠动脉粥样硬化病变的脂质含量，并且我们将诱导B1细胞和抗动脉粥样硬化性抗PC IgM抗体与ILC2s直接联系起来。