IQ motif-containing GTPase-activating protein 1 is essential for the optimal maintenance of lung ILC2s
IQ motif-containing GTPase-activating protein 1 is essential for the optimal maintenance of lung ILC2s
复制标题
含有 IQ 基序的 GTP 酶激活蛋白 1 对于肺 ILC2 的最佳维持至关重要
DOI：
10.1093/intimm/dxz077
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发表时间：
2019
影响因子：
4.4
通讯作者：
Ishii Naoto
中科院分区：
文献类型：
--
作者：
Tayama Shunichi;Okuyama Yuko;Phung Hai The;Asao Atsuko;Kobayashi Shuhei;Musha Tomomi;Machiyama Tomoaki;Sakurai Tsuyoshi;Zhang Chengming;Ushio-Fukai Masuko;Kawabe Takeshi;So Takanori;Ishii Naoto
第2组先天淋巴样细胞（ILC 2）在2型免疫中起关键作用，对各种类型的炎性疾病的发病机制至关重要。含有IQ基序的GTPase-activating protein 1（IQGAP 1）是一种普遍表达的支架蛋白，参与细胞生存和运输等多种细胞功能。虽然IQGAP 1在T和B淋巴细胞中的作用已被揭示，但IQGAP 1在先天性淋巴细胞中的生理意义仍有待阐明。在目前的研究中，我们证明，使用骨髓嵌合体，IQGAP 1的缺陷导致肺ILC 2以细胞内在的方式存活受损，并且Iqgap 1 −/−小鼠在施用木瓜蛋白酶后显示ILC 2的积累减少，从而减少了疾病的病理学。此外，在稳态和炎症条件下，与野生型ILC 2相比，Iqgap 1 −/− ILC 2显示出显著增强的凋亡。这些结果一起首次鉴定了IQGAP 1对于肺中ILC 2的稳态是必需的。
Group 2 innate lymphoid cells (ILC2s) play critical roles in type 2 immunity and are crucial for pathogenesis of various types of inflammatory disease. IQ motif-containing GTPase-activating protein 1 (IQGAP1) is a ubiquitously expressed scaffold protein that is involved in multiple cellular functions such as cell survival and trafficking. While the roles for IQGAP1 in T and B lymphocytes have been uncovered, the physiological significance of IQGAP1 in innate lymphocytes remains to be elucidated. In the current study, we demonstrate that using bone marrow chimeras, the deficiency of IQGAP1 caused an impaired survival of lung ILC2s in a cell-intrinsic manner and thatIqgap1−/−mice displayed decreased accumulation of ILC2s after administration of papain and thereby reduced the pathology of the disease. Moreover,Iqgap1−/−ILC2s showed a significantly enhanced apoptosis as compared to wild-type ILC2s under both steady-state and inflammatory conditions. Together these results identify for the first time that IQGAP1 is essential for homeostasis of ILC2s in the lung.