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TRAF3IP3 at the trans-Golgi network regulates nkt2 maturation via the MEK/ERK signaling pathway

Cellular & Molecular Immunology 2020年第4期17卷 395-406页

作者： Xinwei Zhang Ke Wang Weijia Zhao Li Cao Shusong Zhang Rong Jin Xiuyuan Sun Jie Hao Xiaojun Huang Mingzhao Zhu Hounan Wu Hongshan Zhao Qing Ge Department of Immunology School of Basic Medical SciencesPeking UniversityNHC Key Laboratory of Medical Immunology(Peking University)Beijing 100191China Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation Peking University People’s Hospital&Institute of HematologyBeijing 100044China Key Laboratory of Infection and Immunity Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Peking University Medical and Health Analytical Center Peking University Health Science CenterBeijing 100191China Department of Integration of Chinese and Western Medicine School of Basic Medical SciencesPeking UniversityBeijing 100191China

Thymic natural killer T(nkt)2 cells are a subset of invariant nkt cells with PLZF^(hi)GATA3^(hi)IL-4^(+).The differentiation of nkt2 cells is not fully *** the present study,we report an important role of TRAF3-interacting protein 3(TRAF3IP3)in the functional maturation and expansion of committed nkt2s in thymic *** with T-cell-specific deletion of TRAF3IP3 had decreased thymic nkt2 cells,decreased IL-4-producing peripheral inkts,and defects in response toα-*** selection and high PLZF expression in CD24^(+)CD44^(−) and CCR7^(+)CD44^(−) immature inkts were not *** CD44^(hi)NK1.1^(−) inkts in Traf3ip3^(−/−) mice showed reduced expression of Egr2,PLZF,and IL-17RB,decreased proliferation,and reduced IL-4 production upon *** Egr2 and IL-4 expression was augmented by MEK1/ERK activation in inkts,and TRAF3IP3 at the trans-Golgi network recruited MEK1 and facilitated ERK phosphorylation and nuclear *** βR-regulated bone marrow-derived nonlymphoid cells in the medullary thymic microenvironment were required for MEK/ERK activation and nkt2 *** data demonstrate an important functional maturation process in nkt2 differentiation that is regulated by MEK/ERK signaling at the trans-Golgi network.

关键词： TRAF3IP3 nkt2 cells MEK/ERK signaling Functional maturation

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