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pmid:35172900

Increased oxidative stress contributes to impaired peripheral CD56dimCD57+ NK cells from patients with systemic lupus erythematosus.

Zhimin Lu · Yao Tian · Ziran Bai · Jiaqing Liu · Yan Zhang · Jingjing Qi · Minli Jin · Jie Zhu · Xia Li

Arthritis research & therapy · 2022 doi:10.1186/s13075-022-02731-y

Paper

complete

Experiment

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Data

partial

Analysis

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title
Increased oxidative stress contributes to impaired peripheral CD56dimCD57+ NK cells from patients with systemic lupus erythematosus.
doi
10.1186/s13075-022-02731-y
pmid
35172900
authors array · 9 items
[0]
Zhimin Lu
[1]
Yao Tian
[2]
Ziran Bai
[3]
Jiaqing Liu
[4]
Yan Zhang
[5]
Jingjing Qi
[6]
Minli Jin
[7]
Jie Zhu
[8]
Xia Li
journal
Arthritis research & therapy
year
2022
abstract
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 (CD56bright, CD56dimCD57-, and CD56dimCD57+), 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 CD56dimCD57+ 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 CD56dimCD57+ 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 (H2O2), peripheral CD56dimCD57+ NK cell subset was more prone to undergo apoptosis than CD56dimCD57- 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 CD56dimCD57+ 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 CD56dimCD57+ NK cells may contribute to the impaired ability of eliminating pathogenic CD4+ T cells in SLE.
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The chi-square test or Fisher test was used to compare qualitative values according to distribution. The Student’s unpaired or paired t test was performed to compare two groups for parametric data, and the Mann–Whitney U test or Wilcoxon rank sum test was performed for nonparametric data. The Pearson test or Spearman was used to determine the correlation between variables.
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sections[15] "Statistical analysis" paragraph 2
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The chi-square test or Fisher test was used to compare qualitative values according to distribution. The Student’s unpaired or paired t test was performed to compare two groups for parametric data, and the Mann–Whitney U test or Wilcoxon rank sum test was performed for nonparametric data. The Pearson test or Spearman was used to determine the correlation between variables.
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sections[31] "Availability of data and materials" paragraph 2
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Our study demonstrated a selective loss of mature CD56dimCD57+ NK cell subset in SLE patients, which may caused by preferential apoptosis of this subset under increased oxidative stress in SLE.
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dimCD57-, and CD56dimCD57+), phenotypes, and apoptosis were evaluated with flow cytometer. Mitochon
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ted altered phenotypes, increased endogenous apoptosis and higher levels of mtROS and ROS. In addit
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57+ NK cell subset was more prone to undergo apoptosis than CD56dimCD57- NK cells. Furthermore, thi
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) and SLE patients (n = 4). C Representative flow cytometric plot for NK cell subsets (including CD3−CD56
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LE patients, Annexin-V/7-AAD double staining flow cytometry was applied to detect the proportion of apop
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apoptosis in SLE patients. A Representative flow cytometric plot for apoptosis of NK cells (CD56dimCD57+
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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.\nMETHODS: Blood samples from healthy controls (HCs) and patients with SLE and rheumatoid arthritis (RA) were collected. The NK count, NK subsets (CD56bright, CD56dimCD57-, and CD56dimCD57+), 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).\nRESULTS: 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 CD56dimCD57+ 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 CD56dimCD57+ 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 (H2O2), peripheral CD56dimCD57+ NK cell subset was more prone to undergo apoptosis than CD56dimCD57- NK cells. Furthermore, this NK cell subset from SLE patients exhibited impaired cytotoxicity in response to activated CD4+ T cells in vitro.\nCONCLUSION: Our study demonstrated a selective loss of mature CD56dimCD57+ NK cell subset in SLE patients, which may caused by preferential apoptosis of this subset under increased oxidative stress in SLE. 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