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Control of Germinal...
Control of Germinal Center Localization and Lineage Stability of Follicular Regulatory T Cells by the Blimp1 Transcription Factor
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Shen, Erxia (author)
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- Rabe, Hardis (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för infektionssjukdomar,Institute of Biomedicine, Department of Infectious Medicine
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Luo, Lin (author)
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Wang, Lei (author)
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Wang, Qin (author)
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Yin, Jie (author)
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Yang, Xueying (author)
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Liu, Wenquan (author)
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Sido, Jessica M. (author)
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Nakagawa, Hidetoshi (author)
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Ao, Lin (author)
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Kim, Hye Jung (author)
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Cantor, Harvey (author)
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Leavenworth, Jianmei W. (author)
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(creator_code:org_t)
- Elsevier BV, 2019
- 2019
- English.
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In: Cell Reports. - : Elsevier BV. - 2211-1247. ; 29:7
- Related links:
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http://www.cell.com/...
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https://gup.ub.gu.se...
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https://doi.org/10.1...
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Abstract
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- © 2019 The Author(s) Follicular regulatory T (TFR) cells are a specialized suppressive subset that controls the germinal center (GC) response and maintains humoral self-tolerance. The mechanisms that maintain TFR lineage identity and suppressive activity remain largely unknown. Here, we show that expression of Blimp1 by FoxP3+ TFR cells is essential for TFR lineage stability, entry into the GC, and expression of regulatory activity. Deletion of Blimp1 in TFR cells reduced FoxP3 and CTLA-4 expression and increased pro-inflammatory cytokines and spontaneous production of autoantibodies, including elevated IgE. Maintenance of TFR stability reflected Blimp1-dependent repression of the IL-23R-STAT3 axis and activation of the CD25-STAT5 pathway, while silenced IL-23R-STAT3 or increased STAT5 activation rescued the Blimp1-deficient TFR phenotype. Blimp1-dependent control of CXCR5/CCR7 expression also regulated TFR homing into the GC. These findings uncover a Blimp1-dependent TFR checkpoint that enforces suppressive activity and acts as a gatekeeper of GC entry.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
Keyword
- Blimp1
- follicular helper T cells
- follicular regulatory T cells
- germinal center positioning
- germinal center response
- humoral tolerance
- regulatory T cells
- T lineage stability FR
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Shen, Erxia
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Rabe, Hardis
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Luo, Lin
-
Wang, Lei
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Wang, Qin
-
Yin, Jie
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show more...
-
Yang, Xueying
-
Liu, Wenquan
-
Sido, Jessica M.
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Nakagawa, Hideto ...
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Ao, Lin
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Kim, Hye Jung
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Cantor, Harvey
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Leavenworth, Jia ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Immunology in th ...
- Articles in the publication
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Cell Reports
- By the university
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University of Gothenburg