转化生长因子-β信号传导指导唾液腺中固有淋巴细胞的分化。
Transforming Growth Factor-β Signaling Guides the Differentiation of Innate Lymphoid Cells in Salivary Glands.
作者信息
Cortez Victor S, Cervantes-Barragan Luisa, Robinette Michelle L, Bando Jennifer K, Wang Yaming, Geiger Theresa L, Gilfillan Susan, Fuchs Anja, Vivier Eric, Sun Joe C, Cella Marina, Colonna Marco
机构信息
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63108, USA.
Immunology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
出版信息
Immunity. 2016 May 17;44(5):1127-39. doi: 10.1016/j.immuni.2016.03.007. Epub 2016 May 3.
The signals guiding differentiation of innate lymphoid cells (ILCs) within tissues are not well understood. Salivary gland (SG) ILCs as well as liver and intestinal intraepithelial ILC1 have markers that denote tissue residency and transforming growth factor-β (TGF-β) imprinting. We deleted Tgfbr2 in cells expressing the ILC and NK marker NKp46 and found that SG ILCs were reduced in number. They lost distinct tissue markers, such as CD49a, and the effector molecules TRAIL and CD73. Expression of the transcription factor Eomes, which promotes NK cell differentiation, was elevated. Conversely, Eomes deletion in NKp46(+) cells enhanced TGF-β-imprinting of SG ILCs. Thus, TGF-β induces SG ILC differentiation by suppressing Eomes. TGF-β acted through a JNK-dependent, Smad4-independent pathway. Transcriptome analysis demonstrated that SG ILCs had characteristic of both NK cells and ILC1. Finally, TGF-β imprinting of SG ILCs was synchronized with SG development, highlighting the impact of tissue microenvironment on ILC development.
指导组织内固有淋巴细胞（ILC）分化的信号尚未完全清楚。唾液腺（SG）ILC以及肝脏和肠道上皮内ILC1具有表示组织驻留和转化生长因子-β（TGF-β）印记的标志物。我们在表达ILC和NK标志物NKp46的细胞中删除了Tgfbr2，发现SG ILC的数量减少。它们失去了独特的组织标志物，如CD49a，以及效应分子TRAIL和CD73。促进NK细胞分化的转录因子Eomes的表达升高。相反，在NKp46(+)细胞中删除Eomes增强了SG ILC的TGF-β印记。因此，TGF-β通过抑制Eomes诱导SG ILC分化。TGF-β通过JNK依赖、Smad4非依赖的途径发挥作用。转录组分析表明，SG ILC具有NK细胞和ILC1的特征。最后，SG ILC的TGF-β印记与SG发育同步，突出了组织微环境对ILC发育的影响。
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