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Increased oxidative stress contributes to impaired peripheral CD56(dim)CD57(+) NK cells from patients with systemic lupus erythematosus

BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by loss of immune tolerance and imbalance of immune cell subsets. Natural killer (NK) cells contribute to regulate both the innate and adaptive immune response. In this study, we aimed to detect alterations of peripheral NK cells and ex...

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Autores principales: Lu, Zhimin, Tian, Yao, Bai, Ziran, Liu, Jiaqing, Zhang, Yan, Qi, Jingjing, Jin, Minli, Zhu, Jie, Li, Xia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8848960/
https://www.ncbi.nlm.nih.gov/pubmed/35172900
http://dx.doi.org/10.1186/s13075-022-02731-y
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author Lu, Zhimin
Tian, Yao
Bai, Ziran
Liu, Jiaqing
Zhang, Yan
Qi, Jingjing
Jin, Minli
Zhu, Jie
Li, Xia
author_facet Lu, Zhimin
Tian, Yao
Bai, Ziran
Liu, Jiaqing
Zhang, Yan
Qi, Jingjing
Jin, Minli
Zhu, Jie
Li, Xia
author_sort Lu, Zhimin
collection PubMed
description BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by loss of immune tolerance and imbalance of immune cell subsets. Natural killer (NK) cells contribute to regulate both the innate and adaptive immune response. In this study, we aimed to detect alterations of peripheral NK cells and explore intrinsic mechanisms involving in NK cell abnormality in SLE. METHODS: Blood samples from healthy controls (HCs) and patients with SLE and rheumatoid arthritis (RA) were collected. The NK count, NK subsets (CD56(bright), CD56(dim)CD57(−), and CD56(dim)CD57(+)), phenotypes, and apoptosis were evaluated with flow cytometer. Mitochondrial reactive oxygen species (mtROS) and total ROS levels were detected with MitoSOX Red and DCFH-DA staining respectively. Published data (GSE63829 and GSE23695) from Gene Expression Omnibus (GEO) was analyzed by Gene Set Enrichment Analysis (GSEA). RESULTS: Total peripheral NK count was down-regulated in untreated SLE patients in comparison to that in untreated RA patients and HCs. SLE patients exhibited a selective reduction in peripheral CD56(dim)CD57(+) NK cell proportion, which was negatively associated with disease activity and positively correlated with levels of complement(C)3 and C4. Compared with HCs, peripheral CD56(dim)CD57(+) NK cells from SLE patients exhibited altered phenotypes, increased endogenous apoptosis and higher levels of mtROS and ROS. In addition, when treated with hydrogen peroxide (H(2)O(2)), peripheral CD56(dim)CD57(+) NK cell subset was more prone to undergo apoptosis than CD56(dim)CD57(−) NK cells. Furthermore, this NK cell subset from SLE patients exhibited impaired cytotoxicity in response to activated CD4(+) T cells in vitro. CONCLUSION: Our study demonstrated a selective loss of mature CD56(dim)CD57(+) NK cell subset in SLE patients, which may caused by preferential apoptosis of this subset under increased oxidative stress in SLE. The attenuated in vitro cytotoxicity of CD56(dim)CD57(+) NK cells may contribute to the impaired ability of eliminating pathogenic CD4(+) T cells in SLE. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-022-02731-y.
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spelling pubmed-88489602022-02-18 Increased oxidative stress contributes to impaired peripheral CD56(dim)CD57(+) NK cells from patients with systemic lupus erythematosus Lu, Zhimin Tian, Yao Bai, Ziran Liu, Jiaqing Zhang, Yan Qi, Jingjing Jin, Minli Zhu, Jie Li, Xia Arthritis Res Ther Research Article BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by loss of immune tolerance and imbalance of immune cell subsets. Natural killer (NK) cells contribute to regulate both the innate and adaptive immune response. In this study, we aimed to detect alterations of peripheral NK cells and explore intrinsic mechanisms involving in NK cell abnormality in SLE. METHODS: Blood samples from healthy controls (HCs) and patients with SLE and rheumatoid arthritis (RA) were collected. The NK count, NK subsets (CD56(bright), CD56(dim)CD57(−), and CD56(dim)CD57(+)), phenotypes, and apoptosis were evaluated with flow cytometer. Mitochondrial reactive oxygen species (mtROS) and total ROS levels were detected with MitoSOX Red and DCFH-DA staining respectively. Published data (GSE63829 and GSE23695) from Gene Expression Omnibus (GEO) was analyzed by Gene Set Enrichment Analysis (GSEA). RESULTS: Total peripheral NK count was down-regulated in untreated SLE patients in comparison to that in untreated RA patients and HCs. SLE patients exhibited a selective reduction in peripheral CD56(dim)CD57(+) NK cell proportion, which was negatively associated with disease activity and positively correlated with levels of complement(C)3 and C4. Compared with HCs, peripheral CD56(dim)CD57(+) NK cells from SLE patients exhibited altered phenotypes, increased endogenous apoptosis and higher levels of mtROS and ROS. In addition, when treated with hydrogen peroxide (H(2)O(2)), peripheral CD56(dim)CD57(+) NK cell subset was more prone to undergo apoptosis than CD56(dim)CD57(−) NK cells. Furthermore, this NK cell subset from SLE patients exhibited impaired cytotoxicity in response to activated CD4(+) T cells in vitro. CONCLUSION: Our study demonstrated a selective loss of mature CD56(dim)CD57(+) NK cell subset in SLE patients, which may caused by preferential apoptosis of this subset under increased oxidative stress in SLE. The attenuated in vitro cytotoxicity of CD56(dim)CD57(+) NK cells may contribute to the impaired ability of eliminating pathogenic CD4(+) T cells in SLE. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13075-022-02731-y. BioMed Central 2022-02-16 2022 /pmc/articles/PMC8848960/ /pubmed/35172900 http://dx.doi.org/10.1186/s13075-022-02731-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Lu, Zhimin
Tian, Yao
Bai, Ziran
Liu, Jiaqing
Zhang, Yan
Qi, Jingjing
Jin, Minli
Zhu, Jie
Li, Xia
Increased oxidative stress contributes to impaired peripheral CD56(dim)CD57(+) NK cells from patients with systemic lupus erythematosus
title Increased oxidative stress contributes to impaired peripheral CD56(dim)CD57(+) NK cells from patients with systemic lupus erythematosus
title_full Increased oxidative stress contributes to impaired peripheral CD56(dim)CD57(+) NK cells from patients with systemic lupus erythematosus
title_fullStr Increased oxidative stress contributes to impaired peripheral CD56(dim)CD57(+) NK cells from patients with systemic lupus erythematosus
title_full_unstemmed Increased oxidative stress contributes to impaired peripheral CD56(dim)CD57(+) NK cells from patients with systemic lupus erythematosus
title_short Increased oxidative stress contributes to impaired peripheral CD56(dim)CD57(+) NK cells from patients with systemic lupus erythematosus
title_sort increased oxidative stress contributes to impaired peripheral cd56(dim)cd57(+) nk cells from patients with systemic lupus erythematosus
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8848960/
https://www.ncbi.nlm.nih.gov/pubmed/35172900
http://dx.doi.org/10.1186/s13075-022-02731-y
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