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Single-cell profiling reveals pathogenic role and differentiation trajectory of granzyme K(+)CD8(+) T cells in primary Sjögren’s syndrome

Primary Sjögren’s syndrome (pSS) is a systemic autoimmune inflammatory disease mainly defined by T cell–dominated destruction of exocrine glands. Currently, CD8(+) T cells are thought to be involved in the pathogenesis of pSS. However, the single-cell immune profiling of pSS and molecular signatures...

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Autores principales: Xu, Ting, Zhu, Hao-Xian, You, Xing, Ma, Jin-Fen, Li, Xin, Luo, Pan-Yue, Li, Yang, Lian, Zhe-Xiong, Gao, Cai-Yue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10243796/
https://www.ncbi.nlm.nih.gov/pubmed/36881472
http://dx.doi.org/10.1172/jci.insight.167490
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author Xu, Ting
Zhu, Hao-Xian
You, Xing
Ma, Jin-Fen
Li, Xin
Luo, Pan-Yue
Li, Yang
Lian, Zhe-Xiong
Gao, Cai-Yue
author_facet Xu, Ting
Zhu, Hao-Xian
You, Xing
Ma, Jin-Fen
Li, Xin
Luo, Pan-Yue
Li, Yang
Lian, Zhe-Xiong
Gao, Cai-Yue
author_sort Xu, Ting
collection PubMed
description Primary Sjögren’s syndrome (pSS) is a systemic autoimmune inflammatory disease mainly defined by T cell–dominated destruction of exocrine glands. Currently, CD8(+) T cells are thought to be involved in the pathogenesis of pSS. However, the single-cell immune profiling of pSS and molecular signatures of pathogenic CD8(+) T cells have not been well elucidated. Our multiomics investigation showed that both T cells and B cells, especially CD8(+) T cells, were undergoing significant clonal expansion in pSS patients. TCR clonality analysis revealed that peripheral blood granzyme K(+) (GZMK(+)) CXCR6(+)CD8(+) T cells had higher a proportion of clones shared with CD69(+)CD103(–)CD8(+) tissue-resident memory T (Trm) cells in labial glands in pSS. CD69(+)CD103(–)CD8(+) Trm cells featured by high expression of GZMK were more active and cytotoxic in pSS compared with their CD103(+) counterparts. Peripheral blood GZMK(+)CXCR6(+)CD8(+) T cells with higher CD122 expression were increased and harbored a gene signature similar to Trm cells in pSS. Consistently, IL-15 was significantly elevated in pSS plasma and showed the capacity to promote differentiation of CD8(+) T cells into GZMK(+)CXCR6(+)CD8(+) T cells in a STAT5-dependent manner. In summary, we depicted the immune profile of pSS and further conducted comprehensive bioinformatics analysis and in vitro experimental investigations to characterize the pathogenic role and differentiation trajectory of CD8(+) Trm cells in pSS.
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spelling pubmed-102437962023-06-07 Single-cell profiling reveals pathogenic role and differentiation trajectory of granzyme K(+)CD8(+) T cells in primary Sjögren’s syndrome Xu, Ting Zhu, Hao-Xian You, Xing Ma, Jin-Fen Li, Xin Luo, Pan-Yue Li, Yang Lian, Zhe-Xiong Gao, Cai-Yue JCI Insight Research Article Primary Sjögren’s syndrome (pSS) is a systemic autoimmune inflammatory disease mainly defined by T cell–dominated destruction of exocrine glands. Currently, CD8(+) T cells are thought to be involved in the pathogenesis of pSS. However, the single-cell immune profiling of pSS and molecular signatures of pathogenic CD8(+) T cells have not been well elucidated. Our multiomics investigation showed that both T cells and B cells, especially CD8(+) T cells, were undergoing significant clonal expansion in pSS patients. TCR clonality analysis revealed that peripheral blood granzyme K(+) (GZMK(+)) CXCR6(+)CD8(+) T cells had higher a proportion of clones shared with CD69(+)CD103(–)CD8(+) tissue-resident memory T (Trm) cells in labial glands in pSS. CD69(+)CD103(–)CD8(+) Trm cells featured by high expression of GZMK were more active and cytotoxic in pSS compared with their CD103(+) counterparts. Peripheral blood GZMK(+)CXCR6(+)CD8(+) T cells with higher CD122 expression were increased and harbored a gene signature similar to Trm cells in pSS. Consistently, IL-15 was significantly elevated in pSS plasma and showed the capacity to promote differentiation of CD8(+) T cells into GZMK(+)CXCR6(+)CD8(+) T cells in a STAT5-dependent manner. In summary, we depicted the immune profile of pSS and further conducted comprehensive bioinformatics analysis and in vitro experimental investigations to characterize the pathogenic role and differentiation trajectory of CD8(+) Trm cells in pSS. American Society for Clinical Investigation 2023-04-24 /pmc/articles/PMC10243796/ /pubmed/36881472 http://dx.doi.org/10.1172/jci.insight.167490 Text en © 2023 Xu et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Xu, Ting
Zhu, Hao-Xian
You, Xing
Ma, Jin-Fen
Li, Xin
Luo, Pan-Yue
Li, Yang
Lian, Zhe-Xiong
Gao, Cai-Yue
Single-cell profiling reveals pathogenic role and differentiation trajectory of granzyme K(+)CD8(+) T cells in primary Sjögren’s syndrome
title Single-cell profiling reveals pathogenic role and differentiation trajectory of granzyme K(+)CD8(+) T cells in primary Sjögren’s syndrome
title_full Single-cell profiling reveals pathogenic role and differentiation trajectory of granzyme K(+)CD8(+) T cells in primary Sjögren’s syndrome
title_fullStr Single-cell profiling reveals pathogenic role and differentiation trajectory of granzyme K(+)CD8(+) T cells in primary Sjögren’s syndrome
title_full_unstemmed Single-cell profiling reveals pathogenic role and differentiation trajectory of granzyme K(+)CD8(+) T cells in primary Sjögren’s syndrome
title_short Single-cell profiling reveals pathogenic role and differentiation trajectory of granzyme K(+)CD8(+) T cells in primary Sjögren’s syndrome
title_sort single-cell profiling reveals pathogenic role and differentiation trajectory of granzyme k(+)cd8(+) t cells in primary sjögren’s syndrome
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10243796/
https://www.ncbi.nlm.nih.gov/pubmed/36881472
http://dx.doi.org/10.1172/jci.insight.167490
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