Single cell sequencing identifies clonally expanded synovial CD4         + T         PH cells expressing GPR56 in rheumatoid arthritis.

Alexandra Argyriou; Marc H Wadsworth; Adrian Lendvai; Stephen M Christensen; Aase H Hensvold; Christina Gerstner; Annika van Vollenhoven; Kellie Kravarik; Aaron Winkler; Vivianne Malmström; Karine Chemin

doi:10.1038/s41467-022-31519-6

Single cell sequencing identifies clonally expanded synovial CD4 + T PH cells expressing GPR56 in rheumatoid arthritis.

Alexandra Argyriou, Marc H Wadsworth, Adrian Lendvai, Stephen M Christensen, Aase H Hensvold, Christina Gerstner, Annika van Vollenhoven, Kellie Kravarik, Aaron Winkler, Vivianne Malmström, Karine Chemin

Publikation: Beitrag in Fachzeitschrift › Artikel › Begutachtung

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease affecting synovial joints where different CD4 + T cell subsets may contribute to pathology. Here, we perform single cell sequencing on synovial CD4 + T cells from anti-citrullinated protein antibodies (ACPA)+ and ACPA- RA patients and identify two peripheral helper T cell (T PH) states and a cytotoxic CD4 + T cell subset. We show that the adhesion G-protein coupled receptor 56 (GPR56) delineates synovial CXCL13 high T PH CD4 + T cells expressing LAG-3 and the tissue-resident memory receptors CXCR6 and CD69. In ACPA- SF, T PH cells display lower levels of GPR56 and LAG-3. Further, most expanded T cell clones in the joint are within CXCL13 high T PH CD4 + T cells. Finally, RNA-velocity analyses suggest a common differentiation pathway between the two T PH clusters and effector CD4 + T cells. Our study provides comprehensive immunoprofiling of the synovial CD4 + T cell subsets in ACPA+ and ACPA- RA.

Originalsprache	Englisch
Aufsatznummer	4046
Seiten (von - bis)	4046
Fachzeitschrift	Nature Communications
Jahrgang	13
Ausgabenummer	1
DOIs	https://doi.org/10.1038/s41467-022-31519-6
Publikationsstatus	Veröffentlicht - 13 Juli 2022
Extern publiziert	Ja

IMC Forschungsschwerpunkte

Medical biotechnology

ÖFOS 2012 - Österreichischen Systematik der Wissenschaftszweige

304005 Medizinische Biotechnologie

UN SDGs

Dieser Output leistet einen Beitrag zu folgendem(n) Ziel(en) für nachhaltige Entwicklung

Zugriff auf Dokument

10.1038/s41467-022-31519-6

Andere Dateien und Links

Verknüpfung zur Publikation in Scopus

Dieses zitieren

Argyriou, A., Wadsworth, M. H., Lendvai, A., Christensen, S. M., Hensvold, A. H., Gerstner, C., van Vollenhoven, A., Kravarik, K., Winkler, A., Malmström, V., & Chemin, K. (2022). Single cell sequencing identifies clonally expanded synovial CD4 + T PH cells expressing GPR56 in rheumatoid arthritis. Nature Communications, 13(1), 4046. Artikel 4046. https://doi.org/10.1038/s41467-022-31519-6

@article{ef183e76bd9344a087c3ff4c44f6b530,

title = "Single cell sequencing identifies clonally expanded synovial CD4 + T PH cells expressing GPR56 in rheumatoid arthritis.",

abstract = "Rheumatoid arthritis (RA) is an autoimmune disease affecting synovial joints where different CD4 + T cell subsets may contribute to pathology. Here, we perform single cell sequencing on synovial CD4 + T cells from anti-citrullinated protein antibodies (ACPA)+ and ACPA- RA patients and identify two peripheral helper T cell (T PH) states and a cytotoxic CD4 + T cell subset. We show that the adhesion G-protein coupled receptor 56 (GPR56) delineates synovial CXCL13 high T PH CD4 + T cells expressing LAG-3 and the tissue-resident memory receptors CXCR6 and CD69. In ACPA- SF, T PH cells display lower levels of GPR56 and LAG-3. Further, most expanded T cell clones in the joint are within CXCL13 high T PH CD4 + T cells. Finally, RNA-velocity analyses suggest a common differentiation pathway between the two T PH clusters and effector CD4 + T cells. Our study provides comprehensive immunoprofiling of the synovial CD4 + T cell subsets in ACPA+ and ACPA- RA. ",

keywords = "Arthritis, Rheumatoid/immunology, Humans, Joints/metabolism, Receptors, G-Protein-Coupled/genetics, T-Lymphocyte Subsets/immunology, T-Lymphocytes, Helper-Inducer/immunology",

author = "Alexandra Argyriou and Wadsworth, {Marc H} and Adrian Lendvai and Christensen, {Stephen M} and Hensvold, {Aase H} and Christina Gerstner and {van Vollenhoven}, Annika and Kellie Kravarik and Aaron Winkler and Vivianne Malmstr{\"o}m and Karine Chemin",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = jul,

day = "13",

doi = "10.1038/s41467-022-31519-6",

language = "English",

volume = "13",

pages = "4046",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "Nature Publishing Group",

number = "1",

}

Argyriou, A, Wadsworth, MH, Lendvai, A, Christensen, SM, Hensvold, AH, Gerstner, C, van Vollenhoven, A, Kravarik, K, Winkler, A, Malmström, V & Chemin, K 2022, 'Single cell sequencing identifies clonally expanded synovial CD4 + T PH cells expressing GPR56 in rheumatoid arthritis.', Nature Communications, Jg. 13, Nr. 1, 4046, S. 4046. https://doi.org/10.1038/s41467-022-31519-6

TY - JOUR

T1 - Single cell sequencing identifies clonally expanded synovial CD4 + T PH cells expressing GPR56 in rheumatoid arthritis.

AU - Argyriou, Alexandra

AU - Wadsworth, Marc H

AU - Lendvai, Adrian

AU - Christensen, Stephen M

AU - Hensvold, Aase H

AU - Gerstner, Christina

AU - van Vollenhoven, Annika

AU - Kravarik, Kellie

AU - Winkler, Aaron

AU - Malmström, Vivianne

AU - Chemin, Karine

PY - 2022/7/13

Y1 - 2022/7/13

N2 - Rheumatoid arthritis (RA) is an autoimmune disease affecting synovial joints where different CD4 + T cell subsets may contribute to pathology. Here, we perform single cell sequencing on synovial CD4 + T cells from anti-citrullinated protein antibodies (ACPA)+ and ACPA- RA patients and identify two peripheral helper T cell (T PH) states and a cytotoxic CD4 + T cell subset. We show that the adhesion G-protein coupled receptor 56 (GPR56) delineates synovial CXCL13 high T PH CD4 + T cells expressing LAG-3 and the tissue-resident memory receptors CXCR6 and CD69. In ACPA- SF, T PH cells display lower levels of GPR56 and LAG-3. Further, most expanded T cell clones in the joint are within CXCL13 high T PH CD4 + T cells. Finally, RNA-velocity analyses suggest a common differentiation pathway between the two T PH clusters and effector CD4 + T cells. Our study provides comprehensive immunoprofiling of the synovial CD4 + T cell subsets in ACPA+ and ACPA- RA.

AB - Rheumatoid arthritis (RA) is an autoimmune disease affecting synovial joints where different CD4 + T cell subsets may contribute to pathology. Here, we perform single cell sequencing on synovial CD4 + T cells from anti-citrullinated protein antibodies (ACPA)+ and ACPA- RA patients and identify two peripheral helper T cell (T PH) states and a cytotoxic CD4 + T cell subset. We show that the adhesion G-protein coupled receptor 56 (GPR56) delineates synovial CXCL13 high T PH CD4 + T cells expressing LAG-3 and the tissue-resident memory receptors CXCR6 and CD69. In ACPA- SF, T PH cells display lower levels of GPR56 and LAG-3. Further, most expanded T cell clones in the joint are within CXCL13 high T PH CD4 + T cells. Finally, RNA-velocity analyses suggest a common differentiation pathway between the two T PH clusters and effector CD4 + T cells. Our study provides comprehensive immunoprofiling of the synovial CD4 + T cell subsets in ACPA+ and ACPA- RA.

KW - Arthritis, Rheumatoid/immunology

KW - Humans

KW - Joints/metabolism

KW - Receptors, G-Protein-Coupled/genetics

KW - T-Lymphocyte Subsets/immunology

KW - T-Lymphocytes, Helper-Inducer/immunology

UR - http://www.scopus.com/inward/record.url?scp=85133992094&partnerID=8YFLogxK

U2 - 10.1038/s41467-022-31519-6

DO - 10.1038/s41467-022-31519-6

M3 - Article

C2 - 35831277

SN - 2041-1723

VL - 13

SP - 4046

JO - Nature Communications

JF - Nature Communications

IS - 1

M1 - 4046

ER -