Transcription Factor Bcl11b Controls Identity and Function of Mature Type 2 Innate Lymphoid Cells.
Transcription Factor Bcl11b Controls Identity and Function of Mature Type 2 Innate Lymphoid Cells.
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DOI：
10.1016/j.immuni.2015.07.005
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发表时间：
2015-08-18
期刊：
影响因子：
32.4
通讯作者：
Avram D
中科院分区：
文献类型：
--
作者：
Califano D;Cho JJ;Uddin MN;Lorentsen KJ;Yang Q;Bhandoola A;Li H;Avram D
2型先天淋巴细胞（ILC 2）促进抗蠕虫反应并导致过敏。在这里，我们报告说，Bcl 11b，以前被认为是一个T细胞谱系的身份转录因子，直接上游的关键ILC 2转录因子Gfi 1，以维持其在成熟ILC 2的表达。因此，Bcl 11b −/− ILC 2s下调Gata 3和下游基因，包括编码IL-33受体的Il 1 rl 1，并上调Rorc和3型ILC（ILC 3）基因。此外，独立于Gfi 1，Bcl 11b直接抑制ILC 3转录因子Ahr的表达，进一步导致ILC 2中ILC 3基因的沉默。因此，Bcl 11b −/− ILC 2失去了它们的功能，获得了ILC 3的功能，在对蛋白酶过敏原木瓜蛋白酶的反应中扩增，同时产生ILC 3而不是ILC 2细胞因子，并导致嗜中性粒细胞而不是嗜酸性粒细胞的气道浸润增加。我们的研究结果拓宽了Bcl 11b的作用，从一个T细胞的转录因子，并建立Bcl 11b维持成熟的ILC 2的遗传和功能程序和谱系保真度。
Type-2 innate lymphoid cells (ILC2s) promote anti-helminth responses and contribute to allergies. Here we report that Bcl11b, previously considered a T-cell lineage identity transcription factor, acts directly upstream of the key ILC2 transcription factor Gfi1 to maintain its expression in mature ILC2s. Consequently, Bcl11b−/− ILC2s downregulated Gata3 and downstream genes, including Il1rl1, encoding IL-33 receptor, and upregulated Rorc and type-3 ILC (ILC3) genes. Additionally, independent of Gfi1, Bcl11b directly repressed expression of the ILC3 transcription factor Ahr, further contributing to silencing of ILC3 genes in ILC2s. Thus, Bcl11b−/− ILC2s lost their functions and gained ILC3 functions, expanding in response to the protease allergen papain, while at the same time producing ILC3, and not ILC2 cytokines, and causing increased airway infiltration of neutrophils instead of eosinophils. Our results broaden Bcl11b's role from a T-cell only transcription factor, and establish that Bcl11b sustains mature ILC2 genetic and functional programs and lineage fidelity.