Granulocytic myeloid-derived suppressor cells contribute to IFN-I signaling activation of B cells and disease progression through the lncRNA NEAT1-BAFF axis in systemic lupus erythematosus

Guanjun Dong, Yonghong Yang, Xuehui Li, Xiaoying Yao, Yuzhen Zhu, Hui Zhang, Haiyan Wang, Qun Ma, Junfeng Zhang, Hui Shi, Zhaochen Ning, Fenglian Yan, Weiwei Zhai, Jun Dai, Zhihua Li, Chunxia Li, Jiankuo Ming, Qingjie Xue, Xiangzhi Meng, Chuanping SiHuabao Xiong

Research output: Contribution to journalArticle

Abstract

Activation of interferon (IFN)-I signaling in B cells contributes to the pathogenesis of systemic lupus erythematosus (SLE). Recent studies have shown that myeloid-derived suppressor cells (MDSCs) significantly expand in SLE patients and lupus-prone MRL/lpr mice and contribute to the pathogenesis of SLE. However, the role of SLE-derived MDSCs in regulating IFN-I signaling activation of B cells remains unknown. Here, we demonstrate that expansions of MDSCs, including granulocyte (G)-MDSCs and monocytic (M)-MDSCs, during the progression of SLE were correlated with the IFN-I signature of B cells. Interestingly, G-MDSCs from MRL/lpr mice, but not M-MDSCs, could significantly promote IFN-I signaling activation of B cells and contribute to the pathogenesis of SLE. Mechanistically, we identified that the long non-coding RNA NEAT1 was over-expressed in G-MDSCs from MRL/lpr mice and could induce the promotion of G-MDSCs on IFN-I signaling activation of B cells through B cell-activating factor (BAFF) secretion. Importantly, NEAT1 deficiency significantly attenuated the lupus symptoms in pristane-induced lupus mice. In addition, there was a positive correlation between NEAT1 and BAFF with the IFN signature in SLE patients. In conclusion, G-MDSCs may contribute to the IFN signature in SLE B cells through the NEAT1-BAFF axis, highlighting G-MDSCs as a potential therapeutic target to treat SLE.

Original languageEnglish (US)
Article number165554
JournalBiochimica et Biophysica Acta - Molecular Basis of Disease
Volume1866
Issue number1
DOIs
StatePublished - Jan 1 2020

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Long Noncoding RNA
Systemic Lupus Erythematosus
Interferons
Disease Progression
B-Lymphocytes
Inbred MRL lpr Mouse
Myeloid-Derived Suppressor Cells
B-Cell Activating Factor
Granulocytes

Keywords

  • B cells
  • BAFF
  • lncRNA NEAT1
  • MDSCs
  • SLE

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology

Cite this

Granulocytic myeloid-derived suppressor cells contribute to IFN-I signaling activation of B cells and disease progression through the lncRNA NEAT1-BAFF axis in systemic lupus erythematosus. / Dong, Guanjun; Yang, Yonghong; Li, Xuehui; Yao, Xiaoying; Zhu, Yuzhen; Zhang, Hui; Wang, Haiyan; Ma, Qun; Zhang, Junfeng; Shi, Hui; Ning, Zhaochen; Yan, Fenglian; Zhai, Weiwei; Dai, Jun; Li, Zhihua; Li, Chunxia; Ming, Jiankuo; Xue, Qingjie; Meng, Xiangzhi; Si, Chuanping; Xiong, Huabao.

In: Biochimica et Biophysica Acta - Molecular Basis of Disease, Vol. 1866, No. 1, 165554, 01.01.2020.

Research output: Contribution to journalArticle

Dong, G, Yang, Y, Li, X, Yao, X, Zhu, Y, Zhang, H, Wang, H, Ma, Q, Zhang, J, Shi, H, Ning, Z, Yan, F, Zhai, W, Dai, J, Li, Z, Li, C, Ming, J, Xue, Q, Meng, X, Si, C & Xiong, H 2020, 'Granulocytic myeloid-derived suppressor cells contribute to IFN-I signaling activation of B cells and disease progression through the lncRNA NEAT1-BAFF axis in systemic lupus erythematosus', Biochimica et Biophysica Acta - Molecular Basis of Disease, vol. 1866, no. 1, 165554. https://doi.org/10.1016/j.bbadis.2019.165554
Dong, Guanjun ; Yang, Yonghong ; Li, Xuehui ; Yao, Xiaoying ; Zhu, Yuzhen ; Zhang, Hui ; Wang, Haiyan ; Ma, Qun ; Zhang, Junfeng ; Shi, Hui ; Ning, Zhaochen ; Yan, Fenglian ; Zhai, Weiwei ; Dai, Jun ; Li, Zhihua ; Li, Chunxia ; Ming, Jiankuo ; Xue, Qingjie ; Meng, Xiangzhi ; Si, Chuanping ; Xiong, Huabao. / Granulocytic myeloid-derived suppressor cells contribute to IFN-I signaling activation of B cells and disease progression through the lncRNA NEAT1-BAFF axis in systemic lupus erythematosus. In: Biochimica et Biophysica Acta - Molecular Basis of Disease. 2020 ; Vol. 1866, No. 1.
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abstract = "Activation of interferon (IFN)-I signaling in B cells contributes to the pathogenesis of systemic lupus erythematosus (SLE). Recent studies have shown that myeloid-derived suppressor cells (MDSCs) significantly expand in SLE patients and lupus-prone MRL/lpr mice and contribute to the pathogenesis of SLE. However, the role of SLE-derived MDSCs in regulating IFN-I signaling activation of B cells remains unknown. Here, we demonstrate that expansions of MDSCs, including granulocyte (G)-MDSCs and monocytic (M)-MDSCs, during the progression of SLE were correlated with the IFN-I signature of B cells. Interestingly, G-MDSCs from MRL/lpr mice, but not M-MDSCs, could significantly promote IFN-I signaling activation of B cells and contribute to the pathogenesis of SLE. Mechanistically, we identified that the long non-coding RNA NEAT1 was over-expressed in G-MDSCs from MRL/lpr mice and could induce the promotion of G-MDSCs on IFN-I signaling activation of B cells through B cell-activating factor (BAFF) secretion. Importantly, NEAT1 deficiency significantly attenuated the lupus symptoms in pristane-induced lupus mice. In addition, there was a positive correlation between NEAT1 and BAFF with the IFN signature in SLE patients. In conclusion, G-MDSCs may contribute to the IFN signature in SLE B cells through the NEAT1-BAFF axis, highlighting G-MDSCs as a potential therapeutic target to treat SLE.",
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T1 - Granulocytic myeloid-derived suppressor cells contribute to IFN-I signaling activation of B cells and disease progression through the lncRNA NEAT1-BAFF axis in systemic lupus erythematosus

AU - Dong, Guanjun

AU - Yang, Yonghong

AU - Li, Xuehui

AU - Yao, Xiaoying

AU - Zhu, Yuzhen

AU - Zhang, Hui

AU - Wang, Haiyan

AU - Ma, Qun

AU - Zhang, Junfeng

AU - Shi, Hui

AU - Ning, Zhaochen

AU - Yan, Fenglian

AU - Zhai, Weiwei

AU - Dai, Jun

AU - Li, Zhihua

AU - Li, Chunxia

AU - Ming, Jiankuo

AU - Xue, Qingjie

AU - Meng, Xiangzhi

AU - Si, Chuanping

AU - Xiong, Huabao

PY - 2020/1/1

Y1 - 2020/1/1

N2 - Activation of interferon (IFN)-I signaling in B cells contributes to the pathogenesis of systemic lupus erythematosus (SLE). Recent studies have shown that myeloid-derived suppressor cells (MDSCs) significantly expand in SLE patients and lupus-prone MRL/lpr mice and contribute to the pathogenesis of SLE. However, the role of SLE-derived MDSCs in regulating IFN-I signaling activation of B cells remains unknown. Here, we demonstrate that expansions of MDSCs, including granulocyte (G)-MDSCs and monocytic (M)-MDSCs, during the progression of SLE were correlated with the IFN-I signature of B cells. Interestingly, G-MDSCs from MRL/lpr mice, but not M-MDSCs, could significantly promote IFN-I signaling activation of B cells and contribute to the pathogenesis of SLE. Mechanistically, we identified that the long non-coding RNA NEAT1 was over-expressed in G-MDSCs from MRL/lpr mice and could induce the promotion of G-MDSCs on IFN-I signaling activation of B cells through B cell-activating factor (BAFF) secretion. Importantly, NEAT1 deficiency significantly attenuated the lupus symptoms in pristane-induced lupus mice. In addition, there was a positive correlation between NEAT1 and BAFF with the IFN signature in SLE patients. In conclusion, G-MDSCs may contribute to the IFN signature in SLE B cells through the NEAT1-BAFF axis, highlighting G-MDSCs as a potential therapeutic target to treat SLE.

AB - Activation of interferon (IFN)-I signaling in B cells contributes to the pathogenesis of systemic lupus erythematosus (SLE). Recent studies have shown that myeloid-derived suppressor cells (MDSCs) significantly expand in SLE patients and lupus-prone MRL/lpr mice and contribute to the pathogenesis of SLE. However, the role of SLE-derived MDSCs in regulating IFN-I signaling activation of B cells remains unknown. Here, we demonstrate that expansions of MDSCs, including granulocyte (G)-MDSCs and monocytic (M)-MDSCs, during the progression of SLE were correlated with the IFN-I signature of B cells. Interestingly, G-MDSCs from MRL/lpr mice, but not M-MDSCs, could significantly promote IFN-I signaling activation of B cells and contribute to the pathogenesis of SLE. Mechanistically, we identified that the long non-coding RNA NEAT1 was over-expressed in G-MDSCs from MRL/lpr mice and could induce the promotion of G-MDSCs on IFN-I signaling activation of B cells through B cell-activating factor (BAFF) secretion. Importantly, NEAT1 deficiency significantly attenuated the lupus symptoms in pristane-induced lupus mice. In addition, there was a positive correlation between NEAT1 and BAFF with the IFN signature in SLE patients. In conclusion, G-MDSCs may contribute to the IFN signature in SLE B cells through the NEAT1-BAFF axis, highlighting G-MDSCs as a potential therapeutic target to treat SLE.

KW - B cells

KW - BAFF

KW - lncRNA NEAT1

KW - MDSCs

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