CXCR6 marks a novel subset of T-bet(lo)Eomes(hi) natural killer cells residing in human liver.
CXCR6 marks a novel subset of T-bet(lo)Eomes(hi) natural killer cells residing in human liver.
复制标题
DOI：
10.1038/srep26157
复制
发表时间：
2016-05-23
影响因子：
4.6
通讯作者：
Maini MK
中科院分区：
文献类型：
--
作者：
Stegmann KA;Robertson F;Hansi N;Gill U;Pallant C;Christophides T;Pallett LJ;Peppa D;Dunn C;Fusai G;Male V;Davidson BR;Kennedy P;Maini MK
自然杀伤细胞（NK）在人类肝脏中高度富集，在那里它们可以调节免疫和免疫病理学。我们探讨了他们的肝脏居民子集，不同于传统的骨髓来源的NK。与血液相比，CXCR6 + NK在健康和患病肝脏中显著富集（p <0.0001）。人肝CXCR6 + NK具有不成熟表型（主要为CD56brightCD16 − CD57 −），并表达组织驻留标记物CD69。CXCR6 + NK产生的细胞毒性介质和促炎细胞因子比非肝脏特异性CXCR6 −组分少。相反，CXCR6 + NK可以上调TRAIL，这是肝炎发病机制中的关键死亡配体。CXCR6将肝脏NK分为两个转录上不同的群体：T-bethiEomeslo（CXCR6-）和T-betloEomeshi（CXCR6+）;后者在外周中几乎不存在。小循环CXCR6+亚群主要是T-bethiEomeslo，表明其谱系比CXCR6+肝脏NK更接近CXCR6 −外周。这些数据揭示了人类肝脏驻留的T-betloEomeshi NK的大子集，其特征在于它们的CXCR6的表面表达，适应于肝脏耐受性和可诱导的抗病毒免疫。
Natural killer cells (NK) are highly enriched in the human liver, where they can regulate immunity and immunopathology. We probed them for a liver-resident subset, distinct from conventional bone-marrow-derived NK. CXCR6+ NK were strikingly enriched in healthy and diseased liver compared to blood (p < 0.0001). Human hepatic CXCR6+ NK had an immature phenotype (predominantly CD56brightCD16−CD57−), and expressed the tissue-residency marker CD69. CXCR6+ NK produced fewer cytotoxic mediators and pro-inflammatory cytokines than the non-liver-specific CXCR6− fraction. Instead CXCR6+ NK could upregulate TRAIL, a key death ligand in hepatitis pathogenesis. CXCR6 demarcated liver NK into two transcriptionally distinct populations: T-bethiEomeslo(CXCR6−) and T-betloEomeshi(CXCR6+); the latter was virtually absent in the periphery. The small circulating CXCR6+ subset was predominantly T-bethiEomeslo, suggesting its lineage was closer to CXCR6− peripheral than CXCR6+ liver NK. These data reveal a large subset of human liver-resident T-betloEomeshi NK, distinguished by their surface expression of CXCR6, adapted for hepatic tolerance and inducible anti-viral immunity.