TY - JOUR
T1 - Clonal associations between lymphocyte subsets and functional states in rheumatoid arthritis synovium
AU - Dunlap, Garrett
AU - Wagner, Aaron
AU - Meednu, Nida
AU - Wang, Ruoqiao
AU - Zhang, Fan
AU - Ekabe, Jabea Cyril
AU - Jonsson, Anna Helena
AU - Sakaue, Saori
AU - Nathan, Aparna
AU - Bykerk, Vivian P.
AU - Donlin, Laura T.
AU - Goodman, Susan M.
AU - Firestein, Gary S.
AU - Boyle, David L.
AU - Holers, V. Michael
AU - Moreland, Larry W.
AU - Tabechian, Darren
AU - Pitzalis, Costantino
AU - Filer, Andrew
AU - Raychaudhuri, Soumya
AU - Brenner, Michael B.
AU - Thakar, Juilee
AU - McDavid, Andrew
AU - Rao, Deepak A.
AU - Anolik, Jennifer H.
AU - Wei, Kevin
AU - Accelerating Medicines Partnership Program: Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Network
AU - Sahbudin, Ilfita
N1 - Publisher Copyright:
© The Author(s) 2024.
PY - 2024/6/11
Y1 - 2024/6/11
N2 - Rheumatoid arthritis (RA) is an autoimmune disease involving antigen-specific T and B cells. Here, we perform single-cell RNA and repertoire sequencing on paired synovial tissue and blood samples from 12 seropositive RA patients. We identify clonally expanded CD4 + T cells, including CCL5+ cells and T peripheral helper (Tph) cells, which show a prominent transcriptomic signature of recent activation and effector function. CD8 + T cells show higher oligoclonality than CD4 + T cells, with the largest synovial clones enriched in GZMK+ cells. CD8 + T cells with possibly virus-reactive TCRs are distributed across transcriptomic clusters. In the B cell compartment, NR4A1+ activated B cells, and plasma cells are enriched in the synovium and demonstrate substantial clonal expansion. We identify synovial plasma cells that share BCRs with synovial ABC, memory, and activated B cells. Receptor-ligand analysis predicted IFNG and TNFRSF members as mediators of synovial Tph-B cell interactions. Together, these results reveal clonal relationships between functionally distinct lymphocyte populations that infiltrate the synovium of patients with RA.
AB - Rheumatoid arthritis (RA) is an autoimmune disease involving antigen-specific T and B cells. Here, we perform single-cell RNA and repertoire sequencing on paired synovial tissue and blood samples from 12 seropositive RA patients. We identify clonally expanded CD4 + T cells, including CCL5+ cells and T peripheral helper (Tph) cells, which show a prominent transcriptomic signature of recent activation and effector function. CD8 + T cells show higher oligoclonality than CD4 + T cells, with the largest synovial clones enriched in GZMK+ cells. CD8 + T cells with possibly virus-reactive TCRs are distributed across transcriptomic clusters. In the B cell compartment, NR4A1+ activated B cells, and plasma cells are enriched in the synovium and demonstrate substantial clonal expansion. We identify synovial plasma cells that share BCRs with synovial ABC, memory, and activated B cells. Receptor-ligand analysis predicted IFNG and TNFRSF members as mediators of synovial Tph-B cell interactions. Together, these results reveal clonal relationships between functionally distinct lymphocyte populations that infiltrate the synovium of patients with RA.
UR - http://www.scopus.com/inward/record.url?scp=85195888359&partnerID=8YFLogxK
U2 - 10.1038/s41467-024-49186-0
DO - 10.1038/s41467-024-49186-0
M3 - Article
C2 - 38862501
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4991
ER -