Regulation of the terminal maturation of iNKT cells by mediator complex subunit 23

Invariant natural killer T cells (iNKT cells) are a specific subset of T cells that recognize glycolipid antigens and upon activation rapidly exert effector functions. This unique function is established during iNKT cell development; the detailed mechanisms of this process, however, remain to be elu...

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Published inNature communications Vol. 9; no. 1; pp. 3875 - 15
Main Authors Xu, Yu, Sun, Yang, Shen, Hao, Dai, Yuling, Liu, Haifeng, Li, Ronghong, Zhang, Hongdao, Wu, Ligang, Zhu, Xiaoyan, Liu, Xiaolong
Format Journal Article
LanguageEnglish
Published London Nature Publishing Group UK 24.09.2018
Nature Publishing Group
Nature Portfolio
Subjects
38/1
38/47
38/77
38/88
38/91
42/109
631/136/142
631/250/1619/554/383
631/250/1933
631/250/2502
64/110
64/60
Animals
Anticancer properties
Antigens
Antitumor agents
CD4 antigen
CD8 antigen
Cell activation
Cell differentiation
Cell Differentiation - immunology
Cell Line, Tumor
Clonal deletion
Cytokines
Cytokines - metabolism
Developmental stages
Differentiation (biology)
Female
Gene expression
Gene regulation
Humanities and Social Sciences
Humans
Lymphocytes
Lymphocytes T
Male
Maturation
Mediator Complex - genetics
Mediator Complex - physiology
Metabolism
Mice
Mice, Transgenic
multidisciplinary
Natural killer cells
Natural Killer T-Cells - physiology
Neoplasms - immunology
Primary Cell Culture
RNA polymerase
Roles
Science
Science (multidisciplinary)
Thymocytes
Thymocytes - physiology
Thymus gland
Transcription
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ISSN2041-1723
2041-1723
DOI10.1038/s41467-018-06372-1

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Abstract Invariant natural killer T cells (iNKT cells) are a specific subset of T cells that recognize glycolipid antigens and upon activation rapidly exert effector functions. This unique function is established during iNKT cell development; the detailed mechanisms of this process, however, remain to be elucidated. Here the authors show that deletion of the mediator subunit Med23 in CD4 + CD8 + double positive (DP) thymocytes completely blocks iNKT cell development at stage 2. This dysregulation is accompanied by a bias in the expression of genes related to the regulation of transcription and metabolism, and functional impairment of the cells including the loss of NK cell characteristics, reduced ability to secrete cytokines and attenuated recruitment capacity upon activation. Moreover, Med23 -deficient iNKT cells exhibit impaired anti-tumor activity. Our study identifies Med23 as an essential transcriptional regulator that controls iNKT cell differentiation and terminal maturation. Invariant Natural Killer T cells (iNKT) rapidly exert effector functions upon activation, but the mechanisms of their functional maturation remain to be determined. Here, Xu and colleagues show that the mediator subunit Med23 is a transcriptional regulator controlling iNKT cell terminal maturation.
AbstractList Invariant natural killer T cells (iNKT cells) are a specific subset of T cells that recognize glycolipid antigens and upon activation rapidly exert effector functions. This unique function is established during iNKT cell development; the detailed mechanisms of this process, however, remain to be elucidated. Here the authors show that deletion of the mediator subunit Med23 in CD4 CD8 double positive (DP) thymocytes completely blocks iNKT cell development at stage 2. This dysregulation is accompanied by a bias in the expression of genes related to the regulation of transcription and metabolism, and functional impairment of the cells including the loss of NK cell characteristics, reduced ability to secrete cytokines and attenuated recruitment capacity upon activation. Moreover, Med23-deficient iNKT cells exhibit impaired anti-tumor activity. Our study identifies Med23 as an essential transcriptional regulator that controls iNKT cell differentiation and terminal maturation.
Invariant natural killer T cells (iNKT cells) are a specific subset of T cells that recognize glycolipid antigens and upon activation rapidly exert effector functions. This unique function is established during iNKT cell development; the detailed mechanisms of this process, however, remain to be elucidated. Here the authors show that deletion of the mediator subunit Med23 in CD4+CD8+ double positive (DP) thymocytes completely blocks iNKT cell development at stage 2. This dysregulation is accompanied by a bias in the expression of genes related to the regulation of transcription and metabolism, and functional impairment of the cells including the loss of NK cell characteristics, reduced ability to secrete cytokines and attenuated recruitment capacity upon activation. Moreover, Med23-deficient iNKT cells exhibit impaired anti-tumor activity. Our study identifies Med23 as an essential transcriptional regulator that controls iNKT cell differentiation and terminal maturation.
Invariant natural killer T cells (iNKT cells) are a specific subset of T cells that recognize glycolipid antigens and upon activation rapidly exert effector functions. This unique function is established during iNKT cell development; the detailed mechanisms of this process, however, remain to be elucidated. Here the authors show that deletion of the mediator subunit Med23 in CD4 + CD8 + double positive (DP) thymocytes completely blocks iNKT cell development at stage 2. This dysregulation is accompanied by a bias in the expression of genes related to the regulation of transcription and metabolism, and functional impairment of the cells including the loss of NK cell characteristics, reduced ability to secrete cytokines and attenuated recruitment capacity upon activation. Moreover, Med23 -deficient iNKT cells exhibit impaired anti-tumor activity. Our study identifies Med23 as an essential transcriptional regulator that controls iNKT cell differentiation and terminal maturation.
Invariant natural killer T cells (iNKT cells) are a specific subset of T cells that recognize glycolipid antigens and upon activation rapidly exert effector functions. This unique function is established during iNKT cell development; the detailed mechanisms of this process, however, remain to be elucidated. Here the authors show that deletion of the mediator subunit Med23 in CD4+CD8+ double positive (DP) thymocytes completely blocks iNKT cell development at stage 2. This dysregulation is accompanied by a bias in the expression of genes related to the regulation of transcription and metabolism, and functional impairment of the cells including the loss of NK cell characteristics, reduced ability to secrete cytokines and attenuated recruitment capacity upon activation. Moreover, Med23-deficient iNKT cells exhibit impaired anti-tumor activity. Our study identifies Med23 as an essential transcriptional regulator that controls iNKT cell differentiation and terminal maturation.Invariant natural killer T cells (iNKT cells) are a specific subset of T cells that recognize glycolipid antigens and upon activation rapidly exert effector functions. This unique function is established during iNKT cell development; the detailed mechanisms of this process, however, remain to be elucidated. Here the authors show that deletion of the mediator subunit Med23 in CD4+CD8+ double positive (DP) thymocytes completely blocks iNKT cell development at stage 2. This dysregulation is accompanied by a bias in the expression of genes related to the regulation of transcription and metabolism, and functional impairment of the cells including the loss of NK cell characteristics, reduced ability to secrete cytokines and attenuated recruitment capacity upon activation. Moreover, Med23-deficient iNKT cells exhibit impaired anti-tumor activity. Our study identifies Med23 as an essential transcriptional regulator that controls iNKT cell differentiation and terminal maturation.
Invariant natural killer T cells (iNKT cells) are a specific subset of T cells that recognize glycolipid antigens and upon activation rapidly exert effector functions. This unique function is established during iNKT cell development; the detailed mechanisms of this process, however, remain to be elucidated. Here the authors show that deletion of the mediator subunit Med23 in CD4 + CD8 + double positive (DP) thymocytes completely blocks iNKT cell development at stage 2. This dysregulation is accompanied by a bias in the expression of genes related to the regulation of transcription and metabolism, and functional impairment of the cells including the loss of NK cell characteristics, reduced ability to secrete cytokines and attenuated recruitment capacity upon activation. Moreover, Med23 -deficient iNKT cells exhibit impaired anti-tumor activity. Our study identifies Med23 as an essential transcriptional regulator that controls iNKT cell differentiation and terminal maturation. Invariant Natural Killer T cells (iNKT) rapidly exert effector functions upon activation, but the mechanisms of their functional maturation remain to be determined. Here, Xu and colleagues show that the mediator subunit Med23 is a transcriptional regulator controlling iNKT cell terminal maturation.
Invariant Natural Killer T cells (iNKT) rapidly exert effector functions upon activation, but the mechanisms of their functional maturation remain to be determined. Here, Xu and colleagues show that the mediator subunit Med23 is a transcriptional regulator controlling iNKT cell terminal maturation.
ArticleNumber 3875
Author Dai, Yuling
Xu, Yu
Shen, Hao
Zhang, Hongdao
Liu, Xiaolong
Sun, Yang
Li, Ronghong
Wu, Ligang
Liu, Haifeng
Zhu, Xiaoyan
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PublicationTitleAbbrev Nat Commun
PublicationTitleAlternate Nat Commun
PublicationYear 2018
Publisher Nature Publishing Group UK
Nature Publishing Group
Nature Portfolio
Publisher_xml – name: Nature Publishing Group UK
– name: Nature Publishing Group
– name: Nature Portfolio
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Snippet Invariant natural killer T cells (iNKT cells) are a specific subset of T cells that recognize glycolipid antigens and upon activation rapidly exert effector...
Invariant Natural Killer T cells (iNKT) rapidly exert effector functions upon activation, but the mechanisms of their functional maturation remain to be...
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StartPage 3875
SubjectTerms 38/1
38/47
38/77
38/88
38/91
42/109
631/136/142
631/250/1619/554/383
631/250/1933
631/250/2502
64/110
64/60
Animals
Anticancer properties
Antigens
Antitumor agents
CD4 antigen
CD8 antigen
Cell activation
Cell differentiation
Cell Differentiation - immunology
Cell Line, Tumor
Clonal deletion
Cytokines
Cytokines - metabolism
Developmental stages
Differentiation (biology)
Female
Gene expression
Gene regulation
Humanities and Social Sciences
Humans
Lymphocytes
Lymphocytes T
Male
Maturation
Mediator Complex - genetics
Mediator Complex - physiology
Metabolism
Mice
Mice, Transgenic
multidisciplinary
Natural killer cells
Natural Killer T-Cells - physiology
Neoplasms - immunology
Primary Cell Culture
RNA polymerase
Roles
Science
Science (multidisciplinary)
Thymocytes
Thymocytes - physiology
Thymus gland
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Title Regulation of the terminal maturation of iNKT cells by mediator complex subunit 23
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