Single-cell transcriptomics reveal potent extrafollicular B cell response linked with granzyme K+ CD8 T cell activation in lupus kidney
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Le résumé fourni par la source
Objectives B and T cells constitute the majority of infiltrating lymphocytes in the kidney and represent the local perpetrators in lupus nephritis (LN), but the underlying pathogenic mechanisms are not well elucidated. The aim of this study is to explore the kidney-specific adaptive immune landscape in patients with active LN at the single-cell level. Methods We performed single-cell RNA/B cell receptor (BCR)/T cell receptor (TCR) sequencing analysis on sorting-purified B and T cells from the kidney and paired peripheral blood of patients with active LN, and the periphery of matched controls. Flow cytometry, Assay for Transposase Accessible-sequencing, multiplexed immunohistochemistry and functional studies were performed to validate the transcriptomic results. Results High infiltrations of intrarenal atypical B cells (ABCs) and antibody-secreting cells (ASCs) were identified in the B cell compartment. The single-cell BCR repertoire analysis revealed strong clonal expansion of intrarenal ASCs dominated by IGHG1 and IGHG3 isotypes, accompanied by lower frequencies of heavy-chain and light-chain somatic mutations, compared with the peripheral ASCs. Notably, a unique expansion of IGHG4-59 and clonal overlap between ABCs and ASCs was found in kidney-specific clonotypes. In the T cell compartment, we identified granzyme K (GZMK)+ CD8 T cells as the dominant kidney-associated T cells which shared inflammation- and stress-related gene pathways with ABCs. Intrarenal GZMK+ CD8 T cells highly expressed IFNG and displayed strong communication with ABCs via the type II interferon (IFN) pathway. Intrarenal GZMK+ CD8 T cells and ABCs were largely co-localised within the tertiary lymphoid structure, and GZMK+ CD8 T cells potentially contributed to the differentiation of ABCs via IFN-γ and interleukin-21. Conclusions Our study revealed a potent extrafollicular B cell response linked with overactivation of GZMK+ CD8 T cells in the kidney of patients with LN, which may lead to innovative treatments for LN.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Single-cell transcriptomics reveal potent extrafollicular B cell response linked with granzyme K+ CD8 T cell activation in lupus kidney
- Date Crossref
- 01/03/2025
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Shanghai Jiao Tong University Department of Rheumatology pays non établi dans la noticeUniversité ou école supérieure
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Renji Hospital pays non établi dans la noticeÉtablissement de santé
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University of Chinese Academy of Sciences pays non établi dans la noticeUniversité ou école supérieure
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Institute of Infection and Immunity pays non établi dans la noticeStructure de recherche
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Shanghai Cell Therapy Research Institute pays non établi dans la noticeOrganisation à but non lucratif
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Key Laboratory of Immune Response and Immunotherapy pays non établi dans la noticeStructure de recherche
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Suzhou blood center pays non établi dans la noticeInstitution
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Shanghai Immune Therapy Institute pays non établi dans la noticeStructure de recherche
Department of Rheumatology — Shanghai Jiao Tong University, Renji Hospital et University of Chinese Academy of Sciences, avec 5 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.