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Research Article
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Egr2 and 3 control inflammation, but maintain homeostasis, of PD-1high memory phenotype CD4 T cells

View ORCID ProfileAlistair LJ Symonds, View ORCID ProfileWei Zheng, Tizong Miao, Haiyu Wang, TieShang Wang, Ruth Kiome, View ORCID ProfileXiujuan Hou  Correspondence email, View ORCID ProfileSuling Li  Correspondence email, View ORCID ProfilePing Wang  Correspondence email
Alistair LJ Symonds
1The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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  • ORCID record for Alistair LJ Symonds
Wei Zheng
2Division of Rheumatology, Dong Fang Hospital, Beijing University of Chinese Medicine, Beijing, China
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  • ORCID record for Wei Zheng
Tizong Miao
1The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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Haiyu Wang
2Division of Rheumatology, Dong Fang Hospital, Beijing University of Chinese Medicine, Beijing, China
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TieShang Wang
2Division of Rheumatology, Dong Fang Hospital, Beijing University of Chinese Medicine, Beijing, China
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Ruth Kiome
3Bioscience, Brunel University, Uxbridge, UK
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Xiujuan Hou
2Division of Rheumatology, Dong Fang Hospital, Beijing University of Chinese Medicine, Beijing, China
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  • ORCID record for Xiujuan Hou
  • For correspondence: houxiujuan2008@163.com
Suling Li
3Bioscience, Brunel University, Uxbridge, UK
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  • ORCID record for Suling Li
  • For correspondence: su-ling.li@brunel.ac.uk
Ping Wang
1The Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
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  • ORCID record for Ping Wang
  • For correspondence: p.wang@qmul.ac.uk
Published 24 July 2020. DOI: 10.26508/lsa.202000766
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Abstract

The transcription factors Egr2 and 3 are essential for controlling inflammatory autoimmune responses of memory phenotype (MP) CD4 T cells. However, the mechanism is still unclear. We have now found that the Egr2+ subset (PD-1high MP) of MP CD4 T cells expresses high levels of checkpoint molecules (PD-1 and Lag3) and also markers of effector T cells (CXCR3 and ICAM-1). Egr2/3 are not required for PD-1high MP CD4 cell development but mediate a unique transcriptional programme that effectively controls their inflammatory responses, while promoting homeostatic proliferation and adaptive responses. Egr2 negative PD-1high MP CD4 T cells are impaired in homeostatic proliferation and adaptive responses against viral infection but display inflammatory responses to innate stimulation such as IL-12. PD-1high MP CD4 T cells have recently been implicated in rheumatoid arthritis pathogenesis, and we have now found that Egr2 expression is reduced in PD-1high MP CD4 T cells from patients with active rheumatoid arthritis compared with healthy controls. These findings demonstrate that Egr2/3 control the inflammatory responses of PD-1high MP CD4 T cells and maintain their adaptive immune fitness.

  • Received May 5, 2020.
  • Revision received July 9, 2020.
  • Accepted July 10, 2020.
  • © 2020 Symonds et al.
Creative Commons logoCreative Commons logohttps://creativecommons.org/licenses/by/4.0/

This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).

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Egr2 and 3 regulate PD-1high MP T cells
Alistair LJ Symonds, Wei Zheng, Tizong Miao, Haiyu Wang, TieShang Wang, Ruth Kiome, Xiujuan Hou, Suling Li, Ping Wang
Life Science Alliance Jul 2020, 3 (9) e202000766; DOI: 10.26508/lsa.202000766

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Egr2 and 3 regulate PD-1high MP T cells
Alistair LJ Symonds, Wei Zheng, Tizong Miao, Haiyu Wang, TieShang Wang, Ruth Kiome, Xiujuan Hou, Suling Li, Ping Wang
Life Science Alliance Jul 2020, 3 (9) e202000766; DOI: 10.26508/lsa.202000766
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Volume 3, No. 9
September 2020
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