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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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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