Granzyme K

CD4-Positive T-Lymphocytes / metabolism CD8-Positive T-Lymphocytes / metabolism COVID-19 Cytokines / metabolism Granzymes / metabolism Humans

Journal

Science translational medicine
ISSN: 1946-6242
Titre abrégé: Sci Transl Med
Pays: United States
ID NLM: 101505086

Informations de publication

Date de publication:
15 06 2022
Historique:
entrez: 15 6 2022
pubmed: 16 6 2022
medline: 18 6 2022
Statut: ppublish

Résumé

T cell-derived pro-inflammatory cytokines are a major driver of rheumatoid arthritis (RA) pathogenesis. Although these cytokines have traditionally been attributed to CD4 T cells, we have found that CD8 T cells are notably abundant in synovium and make more interferon (IFN)-γ and nearly as much tumor necrosis factor (TNF) as their CD4 T cell counterparts. Furthermore, using unbiased high-dimensional single-cell RNA-seq and flow cytometric data, we found that the vast majority of synovial tissue and synovial fluid CD8 T cells belong to an effector CD8 T cell population characterized by high expression of granzyme K (GzmK) and low expression of granzyme B (GzmB) and perforin. Functional experiments demonstrate that these GzmK

Identifiants

DOI: 10.1126/scitranslmed.abo0686 PMID: 35704599 PMC: PMC9972878
pubmed: 35704599
doi: 10.1126/scitranslmed.abo0686
pmc: PMC9972878
mid: NIHMS1873158
doi:

Substances chimiques

Cytokines 0
Granzymes EC 3.4.21.-

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

eabo0686

Subventions

Organisme : NIAMS NIH HHS
ID : UH2 AR067685
Pays : United States
Organisme : NIAMS NIH HHS
ID : UM2 AR067678
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG012009
Pays : United States
Organisme : NIAMS NIH HHS
ID : T32 AR007530
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067681
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067688
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067689
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067694
Pays : United States
Organisme : NIAMS NIH HHS
ID : K08 AR077037
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067679
Pays : United States
Organisme : NIAMS NIH HHS
ID : UC2 AR081023
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI111224
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR070253
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR073290
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR063759
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067690
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG009379
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067677
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067676
Pays : United States
Organisme : NIAMS NIH HHS
ID : UH2 AR067691
Pays : United States

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Auteurs

A Helena Jonsson (AH)

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
ORCID: 0000-0002-9558-2474

Fan Zhang (F)

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Center for Data Sciences, Brigham and Women's Hospital, Boston, MA 02115, USA.
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Division of Rheumatology and Center for Health Artificial Intelligence, University of Colorado School of Medicine, Aurora, CO 80045, USA.
ORCID: 0000-0002-6102-2970

Garrett Dunlap (G)

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
ORCID: 0000-0002-2627-0506

Emma Gomez-Rivas (E)

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Gerald F M Watts (GFM)

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Heather J Faust (HJ)

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Karishma Vijay Rupani (KV)

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
ORCID: 0000-0002-4779-8326

Joseph R Mears (JR)

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Center for Data Sciences, Brigham and Women's Hospital, Boston, MA 02115, USA.
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
ORCID: 0000-0002-0259-4055

Nida Meednu (N)

Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center, Rochester, NY 14642, USA.
ORCID: 0000-0002-2868-3339

Runci Wang (R)

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Gregory Keras (G)

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
ORCID: 0000-0002-4965-0755

Jonathan S Coblyn (JS)

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
ORCID: 0000-0002-5251-0219

Elena M Massarotti (EM)

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.

Derrick J Todd (DJ)

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
ORCID: 0000-0003-2290-2235

Jennifer H Anolik (JH)

Division of Allergy, Immunology, and Rheumatology, University of Rochester Medical Center, Rochester, NY 14642, USA.
ORCID: 0000-0002-1450-1549

Andrew McDavid (A)

Department of Biostatistics and Computational Biology, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
ORCID: 0000-0002-6581-1213

Kevin Wei (K)

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
ORCID: 0000-0002-1821-167X

Deepak A Rao (DA)

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
ORCID: 0000-0001-9672-7746

Soumya Raychaudhuri (S)

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
Center for Data Sciences, Brigham and Women's Hospital, Boston, MA 02115, USA.
Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA.
Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Arthritis Research UK Centre for Genetics and Genomics, Centre for Musculoskeletal Research, The University of Manchester, Manchester M13 9PT, UK.
ORCID: 0000-0002-1901-8265

Michael B Brenner (MB)

Division of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
ORCID: 0000-0001-6202-8445

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Classifications MeSH

questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Lymphocytes T CD4+ › Granzyme K
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Lymphocytes T CD8+ › Granzyme K
questionsmedicales.fr › Maladies de l'appareil respiratoire › Infections de l'appareil respiratoire › Pneumopathie infectieuse › Pneumopathie virale › COVID-19 › Granzyme K
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Granzyme K
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Peptide hydrolases › Protéases à sérine › Serine endopeptidases › Granzymes › Granzyme K
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Granzyme K