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孤儿核受体 NR2F6 通过调节 IL-21 抑制 T 滤泡辅助细胞积累。

Orphan Nuclear Receptor NR2F6 Suppresses T Follicular Helper Cell Accumulation through Regulation of IL-21.

机构信息

Institute of Cell Genetics, Department for Genetics and Pharmacology, Medical University of Innsbruck, Peter Mayr Str. 1a, 6020 Innsbruck, Austria.

Division of Developmental Immunology, Biocenter, Medical University of Innsbruck, Innsbruck, Innrain 80, 6020 Innsbruck, Austria.

出版信息

Cell Rep. 2019 Sep 10;28(11):2878-2891.e5. doi: 10.1016/j.celrep.2019.08.024.

DOI:10.1016/j.celrep.2019.08.024
PMID:31509749
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6791812/
Abstract

CD4 T follicular helper (Tfh) cells are specialized in helping B cells during the germinal center (GC) reaction and ultimately promote long-term humoral immunity. Here we report that loss of the nuclear orphan receptor NR2F6 causes enhanced survival and accumulation of Tfh cells, GC B cells, and plasma cells (PCs) following T cell-dependent immunization. Nr2f6-deficient CD4 T cell dysfunction is the primary cause of cell accumulation. Cytokine expression in Nr2f6-deficient Tfh cells is dysregulated, and Il21 expression is enhanced. Mechanistically, NR2F6 binds directly to the interleukin 21 (IL-21) promoter and a conserved noncoding sequence (CNS) near the Il21 gene in resting CD4 T cells. During Tfh cell differentiation, this direct NR2F6 DNA interaction is abolished. Enhanced Tfh cell accumulation in Nr2f6-deficient mice can be reverted by blocking IL-21R signaling. Thus, NR2F6 is a critical negative regulator of IL-21 cytokine production in Tfh cells and prevents excessive Tfh cell accumulation.

摘要

CD4+滤泡辅助性 T 细胞（Tfh）在生发中心（GC）反应期间专门帮助 B 细胞，最终促进长期体液免疫。在这里，我们报告核孤儿受体 NR2F6 的缺失导致 T 细胞依赖性免疫接种后 Tfh 细胞、GC B 细胞和浆细胞（PC）的存活和积累增强。Nr2f6 缺陷型 CD4 T 细胞功能障碍是细胞积累的主要原因。Nr2f6 缺陷型 Tfh 细胞中的细胞因子表达失调，Il21 表达增强。在机制上，NR2F6 直接结合到静止 CD4 T 细胞中的白细胞介素 21（IL-21）启动子和 Il21 基因附近的保守非编码序列（CNS）上。在 Tfh 细胞分化期间，这种直接的 NR2F6 DNA 相互作用被废除。在 Nr2f6 缺陷型小鼠中，通过阻断 IL-21R 信号可以逆转增强的 Tfh 细胞积累。因此，NR2F6 是 Tfh 细胞中 IL-21 细胞因子产生的关键负调节剂，可防止 Tfh 细胞过度积累。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3dc/6899495/7a558bd02497/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3dc/6899495/7bffb037213f/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3dc/6899495/fed2628a8d0e/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3dc/6899495/f6e488dec77d/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3dc/6899495/c24292117f29/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3dc/6899495/5a48e154b7d6/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3dc/6899495/8403564cee95/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3dc/6899495/7a558bd02497/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3dc/6899495/7bffb037213f/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3dc/6899495/fed2628a8d0e/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3dc/6899495/f6e488dec77d/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3dc/6899495/c24292117f29/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3dc/6899495/5a48e154b7d6/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3dc/6899495/8403564cee95/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f3dc/6899495/7a558bd02497/gr6.jpg

相似文献

[1]
Orphan Nuclear Receptor NR2F6 Suppresses T Follicular Helper Cell Accumulation through Regulation of IL-21.

Cell Rep. 2019-9-10

[2]
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[3]
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[4]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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Allergy. 2016-5-25

引用本文的文献

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Cell Death Dis. 2025-2-7

[2]
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Front Immunol. 2025-1-7

[3]
The genetics of resistance to infectious pancreatic necrosis virus in rainbow trout unveiled through survival and virus load data.

Front Genet. 2024-11-19

[4]
The roles of nuclear orphan receptor NR2F6 in anti-viral innate immunity.

PLoS Pathog. 2024-6-3

[5]
Cytokines in Follicular Helper T Cell Biology in Physiologic and Pathologic Conditions.

Immune Netw. 2024-2-14

[6]
Abnormally high expression of D1-like dopamine receptors on lupus CD4 T cells promotes Tfh cell differentiation.

Lupus Sci Med. 2023-8

[7]
Melanoma-intrinsic NR2F6 activity regulates antitumor immunity.

Sci Adv. 2023-7-7

[8]
The regulation of Tfh cell differentiation by β-hydroxybutyrylation modification of transcription factor Bcl6.

Chromosoma. 2023-11

[9]
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Front Immunol. 2022

[10]
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Cancers (Basel). 2021-5-26

本文引用的文献

[1]
The epigenetic regulator ATF7ip inhibits expression, regulating Th17 responses.

J Exp Med. 2019-6-19

[2]
T Follicular Helper Cell Biology: A Decade of Discovery and Diseases.

Immunity. 2019-5-21

[3]
Nuclear receptor NR2F6 inhibition potentiates responses to PD-L1/PD-1 cancer immune checkpoint blockade.

Nat Commun. 2018-4-18

[4]
The Encyclopedia of DNA elements (ENCODE): data portal update.

Nucleic Acids Res. 2018-1-4

[5]
T cells lack IL-2Rα but express decoy IL-1R2 and IL-1Ra and suppress the IL-1-dependent activation of T cells.

Sci Immunol. 2017-9-8

[6]
A new staining protocol for detection of murine antibody-secreting plasma cell subsets by flow cytometry.

Eur J Immunol. 2017-8

[7]
Disruption of Pathogenic Cellular Networks by IL-21 Blockade Leads to Disease Amelioration in Murine Lupus.

J Immunol. 2017-4-1

[8]
A laboratory practical illustrating the use of the ChIP-qPCR method in a robust model: Estrogen receptor alpha immunoprecipitation using Mcf-7 culture cells.

Biochem Mol Biol Educ. 2017-3-4

[9]
Germinal Center B Cell Dynamics.

Immunity. 2016-9-20

[10]
Gender-specific differences in PPARγ regulation of follicular helper T cell responses with estrogen.

Sci Rep. 2016-6-23

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