Abstract
It is well established that natural killer (NK) cells are dysregulated in systemic lupus erythematosus (SLE) patients. However, the functions of NK cells and the mechanisms regulated by them in SLE remain incompletely understood. Patients with SLE were recruited from The First Affiliated Hospital of Nanchang University, and their clinical characteristics and treatments were recorded. The expression levels of T cell immunoglobulin mucin-3 (TIM-3) and programmed cell death protein 1 (PD-1) on NK cells were examined using flow cytometry. The correlations between the increase in TIM-3+PD-1+ NK cells in the SLE patients and clinical traits, including inflammatory markers, auto-antibodies, disease activity and severity of SLE, were examined. The TIM-3+NK cells, PD-1+NK cells and TIM-3+PD-1+ NK cells were significantly increased in the SLE patients. The increase in TIM-3+PD-1+ NK cells in the patients with SLE was associated with erythrocyte sedimentation rate, C-reactive protein, anti-double stranded DNA, anti-ribosomal P, SLE disease activity index and clinical features. The frequency of TIM-3+PD-1+NK cells in SLE patients with a cardiovascular disease (CVD) was significantly lower than that in SLE patients without a CVD. Moreover, the increased TIM-3+PD-1+ NK cells were significantly decreased in SLE patients following treatment. The present study suggested that the increased TIM-3+PD-1+ NK cells were associated with the disease activity and severity of SLE and may play a role in SLE pathogenesis.
Highlights
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the presence of autoantibodies that bind with self-antigens to form immune complexesQing Luo and Yunyuan Kong contributed to this studynatural killer (NK) cells are a subset of mononuclear cells, distinguished from B and T lymphocytes by virtue of their large granular morphology and the fact that they are part of the innate immune system [10]
The mean fluorescence intensity (MFI) of PD-1 on T cell immunoglobulin mucin-3 (TIM-3)+PD-1+ and TIM-3−PD-1+NK cells was significantly elevated in the SLE patients compared with the healthy controls (HC) (P < 0.05) (Fig. 2g, h)
HC, healthy control; MFI, mean fluorescence intensity; NK, natural killer; PD-1, programmed death 1; SLE, systemic lupus erythematosus; TIM-3, T cell immunoglobulin mucin-3 show any notable differences (P < 0.05) (Fig. 2j). These results showed that the proportion of TIM-3+PD-1+ NK cells in SLE patients was higher than that in the HC
Summary
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by the presence of autoantibodies that bind with self-antigens to form immune complexesQing Luo and Yunyuan Kong contributed to this studyNK cells are a subset of mononuclear cells, distinguished from B and T lymphocytes by virtue of their large granular morphology and the fact that they are part of the innate immune system [10]. Several NK cell surface activating receptors and inhibitory receptors have been verified to regulate function of NK cells, which results in NK cells modulating both the innate and adaptive immune responses [11]. Immune checkpoint receptors expressed by immune cells can negatively control their activation, expansion and effector functions via inhibitory signals generated by interacting with their cognate ligands. Our previous studies showed that abnormal expression of T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) on NK cells plays an important role in the pathogenesis of SLE, which suggests that the TIGIT signaling pathway may serve as a potential therapeutic target for treating this disease [12]. The results showed that co-expression of PD-1 and TIM-3 above the median conferred a higher risk of relapse and a poorer 36-month overall survival
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
