Nature子刊:细胞因子调控血液和肠道ILC与T细胞的互作
创作:Jack Chen 审核:爱的抉择 05月26日
  • 人类肠道ILCs与健康和大肠癌组织的T细胞共定位,并在肿瘤和肿瘤相邻区域显示出HLA-DR表达升高;
  • 外周血(PB)ILCs能摄取并处理完整蛋白抗原,但不能诱导抗原特异性T细胞的记忆反应;
  • 虽然离体条件缺乏共刺激分子,但炎症小体相关细胞因子IL-1β和IL-18可诱发肠和PB ILCs的抗原呈递特征;
  • IL-1β/IL-18依赖于NF-κB来驱动PB ILCs上HLA-DR和共刺激分子的表达,有效诱导CD4+ T记忆细胞反应,而这种作用被抗炎细胞因子TGF-β强烈抑制。
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爱的抉择
天然淋巴细胞(ILCs)和辅助T细胞在小鼠体内具有双向调节作用,但ILCs和CD4+ T细胞之间的互作如何影响人体免疫功能尚不清楚。近期发表在《Nature Communications》的文章,揭示出细胞因子IL-1β和IL-18通过调控人外周血和肠道ILCs的抗原呈递特征,进而诱导抗原特异性CD4+ T记忆细胞的激活。这说明循环和组织内ILCs具有对细胞因子作出反应及调节局部CD4+ T细胞反应的内在能力,或对肿瘤和炎症治疗具有潜在意义。
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Cytokines regulate the antigen-presenting characteristics of human circulating and tissue-resident intestinal ILCs

细胞因子调节人循环和组织驻留肠道ILCs的抗原呈递特征

10.1038/s41467-020-15695-x

04-27, Article

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ILCs and T helper cells have been shown to exert bi-directional regulation in mice. However, how crosstalk between ILCs and CD4+ T cells influences immune function in humans is unknown. Here we show that human intestinal ILCs co-localize with T cells in healthy and colorectal cancer tissue and display elevated HLA-DR expression in tumor and tumor-adjacent areas. Although mostly lacking co-stimulatory molecules ex vivo, intestinal and peripheral blood (PB) ILCs acquire antigen-presenting characteristics triggered by inflammasome-associated cytokines IL-1β and IL-18. IL-1β drives the expression of HLA-DR and co-stimulatory molecules on PB ILCs in an NF-κB-dependent manner, priming them as efficient inducers of cytomegalovirus-specific memory CD4+ T-cell responses. This effect is strongly inhibited by the anti-inflammatory cytokine TGF-β. Our results suggest that circulating and tissue-resident ILCs have the intrinsic capacity to respond to the immediate cytokine milieu and regulate local CD4+ T-cell responses, with potential implications for anti-tumor immunity and inflammation.

First Authors:
Anna Rao

Correspondence Authors:
Anna Rao,Jenny Mjösberg

All Authors:
Anna Rao,Otto Strauss,Efthymia Kokkinou,Mélanie Bruchard,Kumar P Tripathi,Heinrich Schlums,Anna Carrasco,Luca Mazzurana,Viktoria Konya,Eduardo J Villablanca,Niklas K Björkström,Ulrik Lindforss,Hergen Spits,Jenny Mjösberg

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