Evidence map›Paper›PMID 27503069›Full record

ArticleThe Journal of experimental medicine2016

Ubiquitin ligase MARCH 8 cooperates with CD83 to control surface MHC II expression in thymic epithelium and CD4 T cell selection.

Haiyin Liu, Reema Jain, Jing Guan, Vivian Vuong, Satoshi Ishido, Nicole L La Gruta, Daniel H Gray, Jose A Villadangos, Justine D Mintern

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
3.4field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

48 citing papers in PubMed, 73 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. MARCH E3 Ligases: Understudied Regulators of Pulmonary Immune Function.Journal of respiratory biology and translational medicine · 2026
    Article
  7. Article
  8. Proteostasis of immune checkpoint receptors.The Biochemical journal · 2025
    Review
  9. CD83 suppresses endogenous March-I-dependent MHC class II ubiquitination, endocytosis, and degradation.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. The Function of Ubiquitination in T-Cell Development.Advances in experimental medicine and biology · 2024
    Review
  16. Review
  17. Review
  18. CD83 Regulates the Immune Responses in Inflammatory Disorders.International journal of molecular sciences · 2023
    Review
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Haiyin LiuDepartment of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia.ORCID 0000-0003-3103-6949
Reema JainDepartment of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.ORCID 0000-0002-8100-9300
Jing GuanDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010, Australia Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
Vivian VuongDepartment of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia.ORCID 0000-0002-1389-1514
Satoshi IshidoLaboratory of Integrative Infection Immunity, Showa Pharmaceutical University, Machida, Tokyo 194-0042, Japan Department of Microbiology, Hyogo College of Medicine, Hyogo 663-8131, Japan.ORCID 0000-0002-4447-8853
Nicole L La GrutaDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010, Australia Infection and Immunity Program, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia.
Daniel H GrayDepartment of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
Jose A VilladangosDepartment of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Parkville, Victoria 3010, Australia jmintern@unimelb.edu.au j.villadangos@unimelb.edu.au.ORCID 0000-0001-6771-8891
Justine D MinternDepartment of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria 3010, Australia jmintern@unimelb.edu.au j.villadangos@unimelb.edu.au.
The University of Melbourne · AUHyogo Medical University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Major histocompatibility complex class II (MHC II) expression is tightly regulated, being subjected to cell type-specific mechanisms that closely control its levels at the cell surface. Ubiquitination by the E3 ubiquitin ligase MARCH 1 regulates MHC II expression in dendritic cells and B cells. In this study, we demonstrate that the related ligase MARCH 8 is responsible for regulating surface MHC II in thymic epithelial cells (TECs). March8(-/-) mice have elevated MHC II at the surface of cortical TECs and autoimmune regulator (AIRE)(-) medullary TECs (mTECs), but not AIRE(+) mTECs. Despite this, thymic and splenic CD4(+) T cell numbers and repertoires remained unaltered in March8(-/-) mice. Notably, the ubiquitination of MHC II by MARCH 8 is controlled by CD83. Mice expressing a mutated form of CD83 (Cd83(anu/anu) mice) have impaired CD4(+) T cell selection, but deleting March8 in Cd83(anu/anu) mice restored CD4(+) T cell selection to normal levels. Therefore, orchestrated regulation of MHC II surface expression in TECs by MARCH 8 and CD83 plays a major role in CD4(+) T cell selection. Our results also highlight the specialized use of ubiquitinating machinery in distinct antigen-presenting cell types, with important functional consequences and implications for therapeutic manipulation.

Indexed as

AnimalsAntigens, CDCD4-Positive T-LymphocytesCD83 AntigenEpithelial CellsHistocompatibility Antigens Class IIImmunoglobulinsMembrane GlycoproteinsMiceMice, Inbred C57BLThymus GlandUbiquitinationUbiquitin-Protein LigasesAntigens, CDCD83 AntigenHistocompatibility Antigens Class IIImmunoglobulinsMarch8 protein, mouseMembrane GlycoproteinsUbiquitin-Protein Ligases

Identifiers

PMID27503069
PMCPMC4995085
OpenAlexW2509062760

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.