Cutting Edge: Eomesodermin Is Sufficient To Direct Type 1 Innate Lymphocyte Development into the Conventional NK Lineage.
Cutting Edge: Eomesodermin Is Sufficient To Direct Type 1 Innate Lymphocyte Development into the Conventional NK Lineage.
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DOI：
10.4049/jimmunol.1502396
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发表时间：
2016-02-15
期刊：
影响因子：
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通讯作者：
Reiner SL
中科院分区：
文献类型：
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作者：
Pikovskaya O;Chaix J;Rothman NJ;Collins A;Chen YH;Scipioni AM;Vivier E;Reiner SL
1型先天淋巴细胞包括两种发育上不同的谱系，1型辅助先天淋巴细胞（hILC 1）和常规NK细胞（cNK）。所有1型先天淋巴细胞（ILC）表达转录因子T-bet，但cNK还表达Eomesodermin（Eomes）。我们表明，删除Eomes等位基因在1型ILC成熟的发病时，使用NKp 46-Cre在cNK发展中施加了实质性的阻滞。整个淋巴和非淋巴1型ILC区室的形成似乎需要T-bet和Eomes的半冗余作用。为了确定Eomes是否足以将hILC 1发育重定向为cNK命运，我们使用Tbx 21基因座对照来驱动Eomes密码子的表达，在T-bet表达的时间和位置产生表达Eomes的转基因小鼠。异位Eomes诱导跨淋巴和非淋巴1型ILC隔室的cNK样性质。继其不同的谱系特化，hILC 1和cNKs因此具有实质性的发育可塑性。
Type 1 innate lymphocytes comprise two developmentally divergent lineages, type 1 helper innate lymphoid cells (hILC1s) and conventional NK cells (cNKs). All type 1 innate lymphocytes (ILCs) express the transcription factor T-bet, but cNKs additionally express Eomesodermin (Eomes). We show that deletion of Eomes alleles at the onset of type 1 ILC maturation using NKp46-Cre imposes a substantial block in cNK development. Formation of the entire lymphoid and non-lymphoid type 1 ILC compartment appears to require the semi-redundant action of both T-bet and Eomes. To determine if Eomes is sufficient to redirect hILC1 development to a cNK fate, we generated transgenic mice that express Eomes when and where T-bet is expressed using Tbx21 locus control to drive expression of Eomes codons. Ectopic Eomes induces cNK-like properties across the lymphoid and non-lymphoid type 1 ILC compartments. Subsequent to their divergent lineage specification, hILC1s and cNKs thus possess substantial developmental plasticity.