Single-cell transcriptomics reveals granzyme K–expressing cytotoxic Tfh cells in tertiary lymphoid structures in IgG4-RD - 05/02/24
Graphical abstract |
Abstract |
Background |
Germinal center (GC) responses controlled by T follicular helper (Tfh) and T follicular regulatory (Tfr) cells are crucial for the generation of high-affinity antibodies. Acquired immune responses to tissue-released antigens might be mainly induced in tertiary lymphoid organs (TLOs) with GCs in affected tissues. IgG4-related disease (IgG4-RD) demonstrates polarized isotype switching and TLOs in affected tissues. We performed single-cell transcriptomics of tissue-infiltrating T cells from these TLOs to obtain a comprehensive, unbiased view of tissue-infiltrating GC-Tfh cells.
Objective |
To identify GC-Tfh-cell subsets in TLOs in patients with IgG4-RD using single-cell transcriptomics.
Methods |
Single-cell RNA sequencing of sorted CD3+ T cells and multicolor immunofluorescence analysis were used to investigate CD4+CXCR5+Bcl6+ GC-Tfh cells in affected lesions from patients with IgG4-RD.
Results |
Infiltrating CD4+CXCR5+Bcl6+ Tfh cells were divided into 5 main clusters. We detected HLA+ granzyme K+ (GZMK+) Tfh cells with cytotoxicity-associated features in patients with IgG4-RD. We also observed abundant infiltrating Tfr cells with suppressor-associated features in patients with IgG4-RD. These GZMK+ Tfh cells and Tfr cells clustered together in affected tissues from patients with IgG4-RD.
Conclusions |
This single-cell data set revealed a novel subset of HLA+GZMK+ cytotoxic Tfh cells infiltrating affected organs in patients with IgG4-RD, suggesting that infiltrating Tfr cells might suppress cytotoxic Tfh cells.
El texto completo de este artículo está disponible en PDF.Key words : Single-cell RNA sequencing, IgG4-related disease, germinal center, granzyme K, T follicular helper cells, T follicular regulatory cells
Abbreviations used : COVID-19, CTL, GC, GZMB/GZMK, IgG4-RD, scRNA-seq, SG, SjS, SMG, Tfh, Tfr, TLO
Esquema
Vol 153 - N° 2
P. 513 - février 2024 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.
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