The RIG-I pathway is involved in peripheral T cell lymphopenia in patients with dermatomyositis

Abstract Background Peripheral T cell lymphopenia is a clinical phenomenon in some patients with dermatomyositis (DM). Patients with T cell lymphopenia are more susceptible to life-threatening infections. However, the pathogenesis of T cell lymphopenia remains unclear. In this study, we aimed to det...

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Main Authors: Lu Zhang, Qisheng Xia, Wenli Li, Qinglin Peng, Hanbo Yang, Xin Lu, Guochun Wang
Format: Article
Language:English
Published: BMC 2019-05-01
Series:Arthritis Research & Therapy
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13075-019-1905-z
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spelling doaj-1deed50eb906484aac7ee859121182832020-11-25T03:18:09ZengBMCArthritis Research & Therapy1478-63622019-05-0121111210.1186/s13075-019-1905-zThe RIG-I pathway is involved in peripheral T cell lymphopenia in patients with dermatomyositisLu Zhang0Qisheng Xia1Wenli Li2Qinglin Peng3Hanbo Yang4Xin Lu5Guochun Wang6Department of Rheumatology, Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship HospitalInstitute of Clinical Medical Sciences, China-Japan Friendship HospitalDepartment of Rheumatology, Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship HospitalDepartment of Rheumatology, Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship HospitalDepartment of Rheumatology, Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship HospitalDepartment of Rheumatology, Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship HospitalDepartment of Rheumatology, Beijing Key Lab for Immune-Mediated Inflammatory Diseases, China-Japan Friendship HospitalAbstract Background Peripheral T cell lymphopenia is a clinical phenomenon in some patients with dermatomyositis (DM). Patients with T cell lymphopenia are more susceptible to life-threatening infections. However, the pathogenesis of T cell lymphopenia remains unclear. In this study, we aimed to determine retinoic acid-inducible gene I (RIG-I) expression in peripheral T lymphocytes and explore the correlation between RIG-I and T cell lymphopenia in DM. Methods The mRNA and protein expression levels of RIG-I were determined in peripheral T lymphocytes of 26 treatment-naive DM patients by q-PCR and Western blot. The apoptosis of peripheral T lymphocytes was detected by flow cytometry. The associations between RIG-I expression levels and clinical characteristics were investigated. In Jurkat cell, we examined the relationship between RIG-I and cell apoptosis following RIG-I overexpression or activation by specific ligand (pppRNA). The CRISPR/Cas9 gene editing system was used for RIG-I knockout. Fas and caspase 3 were identified by Western blot. CCK8 colorimeter was performed to monitor cell proliferation. Results In DM patients, we observed the peripheral T lymphocyte count decreased notably while the apoptosis of T lymphocytes increased significantly compared with healthy control. RIG-I expression levels in peripheral T cell correlated negatively with T cell count in DM patients. RIG-I protein expression decreased significantly, and the number of T cell increased when disease was improved. In Jurkat cells, increased apoptosis and elevated expression of Fas and cleaved-caspase 3 protein were observed following RIG-I overexpression or RIG-I-specific ligand (pppRNA) activation. Meanwhile, the proliferation of Jurkat cells was markedly reduced. Whereas, neither cell apoptosis nor the cell viability of the RIG-I knockout clones exhibited significant changes following pppRNA activation. Conclusion Our study showed for the first time that negative correlation between the increased RIG-I expression in peripheral T lymphocyte and T cell count in some patients with DM. We demonstrated that highly expressed RIG-I played a critical role in inducing apoptosis and inhibiting proliferation of T lymphocyte in vitro. Therefore, RIG-I-mediated apoptosis may be one of the possible mechanisms of T cell lymphopenia in some patients with DM. These findings expand our existing knowledge on the mechanisms of innate immunity in pathogenesis and provide new therapeutic avenues for DM.http://link.springer.com/article/10.1186/s13075-019-1905-zRIG-IT cell lymphopeniaApoptosisDermatomyositis
collection DOAJ
language English
format Article
sources DOAJ
author Lu Zhang
Qisheng Xia
Wenli Li
Qinglin Peng
Hanbo Yang
Xin Lu
Guochun Wang
spellingShingle Lu Zhang
Qisheng Xia
Wenli Li
Qinglin Peng
Hanbo Yang
Xin Lu
Guochun Wang
The RIG-I pathway is involved in peripheral T cell lymphopenia in patients with dermatomyositis
Arthritis Research & Therapy
RIG-I
T cell lymphopenia
Apoptosis
Dermatomyositis
author_facet Lu Zhang
Qisheng Xia
Wenli Li
Qinglin Peng
Hanbo Yang
Xin Lu
Guochun Wang
author_sort Lu Zhang
title The RIG-I pathway is involved in peripheral T cell lymphopenia in patients with dermatomyositis
title_short The RIG-I pathway is involved in peripheral T cell lymphopenia in patients with dermatomyositis
title_full The RIG-I pathway is involved in peripheral T cell lymphopenia in patients with dermatomyositis
title_fullStr The RIG-I pathway is involved in peripheral T cell lymphopenia in patients with dermatomyositis
title_full_unstemmed The RIG-I pathway is involved in peripheral T cell lymphopenia in patients with dermatomyositis
title_sort rig-i pathway is involved in peripheral t cell lymphopenia in patients with dermatomyositis
publisher BMC
series Arthritis Research & Therapy
issn 1478-6362
publishDate 2019-05-01
description Abstract Background Peripheral T cell lymphopenia is a clinical phenomenon in some patients with dermatomyositis (DM). Patients with T cell lymphopenia are more susceptible to life-threatening infections. However, the pathogenesis of T cell lymphopenia remains unclear. In this study, we aimed to determine retinoic acid-inducible gene I (RIG-I) expression in peripheral T lymphocytes and explore the correlation between RIG-I and T cell lymphopenia in DM. Methods The mRNA and protein expression levels of RIG-I were determined in peripheral T lymphocytes of 26 treatment-naive DM patients by q-PCR and Western blot. The apoptosis of peripheral T lymphocytes was detected by flow cytometry. The associations between RIG-I expression levels and clinical characteristics were investigated. In Jurkat cell, we examined the relationship between RIG-I and cell apoptosis following RIG-I overexpression or activation by specific ligand (pppRNA). The CRISPR/Cas9 gene editing system was used for RIG-I knockout. Fas and caspase 3 were identified by Western blot. CCK8 colorimeter was performed to monitor cell proliferation. Results In DM patients, we observed the peripheral T lymphocyte count decreased notably while the apoptosis of T lymphocytes increased significantly compared with healthy control. RIG-I expression levels in peripheral T cell correlated negatively with T cell count in DM patients. RIG-I protein expression decreased significantly, and the number of T cell increased when disease was improved. In Jurkat cells, increased apoptosis and elevated expression of Fas and cleaved-caspase 3 protein were observed following RIG-I overexpression or RIG-I-specific ligand (pppRNA) activation. Meanwhile, the proliferation of Jurkat cells was markedly reduced. Whereas, neither cell apoptosis nor the cell viability of the RIG-I knockout clones exhibited significant changes following pppRNA activation. Conclusion Our study showed for the first time that negative correlation between the increased RIG-I expression in peripheral T lymphocyte and T cell count in some patients with DM. We demonstrated that highly expressed RIG-I played a critical role in inducing apoptosis and inhibiting proliferation of T lymphocyte in vitro. Therefore, RIG-I-mediated apoptosis may be one of the possible mechanisms of T cell lymphopenia in some patients with DM. These findings expand our existing knowledge on the mechanisms of innate immunity in pathogenesis and provide new therapeutic avenues for DM.
topic RIG-I
T cell lymphopenia
Apoptosis
Dermatomyositis
url http://link.springer.com/article/10.1186/s13075-019-1905-z
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