DOCK8 controls survival of group 3 innate lymphoid cells in the gut through Cdc42 activation
-
- 相原, 良亮
- 九州大学生体防御医学研究所 九州大学大学院歯学研究院
-
- 國村, 和史
- 九州大学生体防御医学研究所
-
- 渡邉, 真裕紀
- 九州大学生体防御医学研究所 日本医療研究開発機構
-
- 宇留野, 武人
- 九州大学生体防御医学研究所
-
- 山根, 奈々
- Division of Immunogenetics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University
-
- 櫻井, 哲哉
- 九州大学生体防御医学研究所
-
- 坂田, 大治
- 九州大学生体防御医学研究所
-
- 西村, 英紀
- 九州大学大学院歯学研究院
-
- 福井, 宣規
- 九州大学大学院歯学研究院
この論文をさがす
抄録
Innate lymphoid cells (ILCs) are a family of developmentally related leukocytes that rapidly secrete polarized sets of cytokines to combat infection and promote tissue repair at mucosal barriers. Among them, group 3 ILCs (ILC3s) play an important role in maintenance of the gut homeostasis by producing IL-22, and their development and function critically depend on the transcription factor RORγt. Although recent evidence indicates that RORγt+ ILC3s are reduced in the gut in the absence of the Cdc42 activator DOCK8 (dedicator of cytokinesis 8), the underlying mechanism remains unclear. We found that genetic deletion of Dock8 in RORγt+-lineage cells markedly reduced ILC3s in the lamina propria of the small intestine. By analyzing BrdU incorporation, it was revealed that DOCK8 deficiency did not affect the cell proliferation. Furthermore, when lineage marker-negative (Lin–) α4β7+ CD127+ RORγt– fetal liver cells were cultured with OP9 stromal cells in the presence of stem cell factor (SCF) and IL-7 in vitro, RORγt+ ILC3s normally developed irrespective of DOCK8 expression. However, DOCK8-deficient ILC3s exhibited a severe defect in survival of ILC3s under the condition with or without IL-7. Similar defects were observed when we analyzed Dock8VAGR mice having mutations in the catalytic center of DOCK8, thereby failing to activate Cdc42. Thus, DOCK8 acts in cell-autonomous manner to control survival of ILC3s in the gut through Cdc42 activation.
収録刊行物
-
- International immunology
-
International immunology 33 (3), 149-160, 2020-09-28
Oxford University Press
- Tweet
詳細情報 詳細情報について
-
- CRID
- 1050017057727081344
-
- NII論文ID
- 120007166274
-
- NII書誌ID
- AA12096432
-
- ISSN
- 14602377
- 09538178
-
- HANDLE
- 2324/4495853
-
- 本文言語コード
- en
-
- 資料種別
- journal article
-
- データソース種別
-
- IRDB
- CiNii Articles