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Lkb1 in dendritic cells restricts CD8(+)Foxp3(+)regulatory T cells expansion in vivo

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机构: [a]Fujian Medical University, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China [b]State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin, 300020, China [c]Department of Hematology, The First Affiliated Hospital of Kunming Medical University, Hematology Research Center of Yunnan Province, Kunming, 650032, China d Central Laboratory, Fujian Medical University Union Hospital, Fuzhou, China
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关键词: Lkb1 Dendritic cells CD8(+)Tregs OX40/OX40L

摘要:
Liver kinase B1 (Lkb1) in dendritic cells (DCs) plays a key role in maintaining immunity homeostasis and adaptive immunity by controlling the CD4(+)Foxp3(+)T regulatory cell (CD4(+) Tregs) pool and T cells activation. However, the function of Lkb1 in DCs for the regulation of CD8(+)Foxp3(+)T regulatory cells (CD8(+)Tregs) has not been addressed. Herein, we found that Lkb1-deficient DCs could lead to excessive CD8(+)Tregs expansion in multiple organs. We found that OX40 expression was significantly higher in Lkb1-deficient DCs compared with that in wild-type (WT) mice, suggesting a potential pathway of CD8(+)Treg expansion. Moreover, we found that CD8(+)Tregs from mice with conditional deletion Lkb1 in DCs (KO) displayed an activated phenotype and expressed higher levels of specific markers, including ICOS and CD103. Interestingly, compared with the WT mice without lipopolysaccharide(LPS) treatment, we found that CD8(+)Tregs population increased in the WT mice with LPS treatment which can selectively delete Lkb1 protein in DCs. However, there was no significant difference in CD8(+)Tregs population in the KO mice between LPS treatment group and non-LPS treatment. Collectively, our findings identified Lkb1 in DCs as a crucial regulator of CD8(+) Treg expansion.

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出版当年[2020]版:
大类 | 3 区 医学
小类 | 3 区 肿瘤学 4 区 细胞生物学
最新[2023]版:
大类 | 3 区 生物学
小类 | 4 区 细胞生物学 4 区 肿瘤学
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出版当年[2019]版:
Q2 ONCOLOGY Q3 CELL BIOLOGY
最新[2023]版:
Q2 ONCOLOGY Q3 CELL BIOLOGY

影响因子: 最新[2023版] 最新五年平均 出版当年[2019版] 出版当年五年平均 出版前一年[2018版] 出版后一年[2020版]

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第一作者机构: [a]Fujian Medical University, Fujian Institute of Hematology, Fujian Provincial Key Laboratory on Hematology, Fujian Medical University Union Hospital, Fuzhou, China
通讯作者:
通讯机构: [*1]Fujian Medical University, Central Laboratory, Fujian Medical University Union Hospital, Fuzhou, China. [*2]State Key Laboratory of Experimental Hematology, Institute of hematology and Hospital of Blood Disease, Chinese Academy of Medical Sciences, 288 Nanjing Road, Tianjin, 300020, China.
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