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

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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13075-019-1905-z) contains supplementary material, which is available to authorized users.