RESUMO
BACKGROUND: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder with varied clinical courses and prognoses, not only did the patients suffer from physical impairment, but also various physical and psychiatric comorbidities. Growing evidence have suggested that mental disorders in SLE patients, can lead to various adverse consequences. AIM: To explored the features and influencing factors of mental health in patients with SLE and clarifying the correlations between mental health and personality characteristics and perceived social support. The results would provide a basis for psychological intervention in patients with SLE. METHODS: The clinical data of 168 patients with SLE admitted at the First Affiliated Hospital of Hainan Medical University between June 2020 and June 2022 were collected. Psychological assessment and correlation analysis were conducted using the Symptom Checklist-90 (SCL-90) and Perceived Social Support Scale, and the collected data were compared with the national norms in China. The relevant factors influencing mental health were identified by statistical analysis. A general information questionnaire, the Revised Life Orientation Test, and Short-Form 36-Item Health Survey were employed to assess optimism level and quality of life (QoL), respectively. RESULTS: Patients with SLE obtained higher scores for the somatization, depression, anxiety, and phobic anxiety subscales than national norms (P < 0.05). A correlation was identified between total social support and total SCL-90 score or each subscale (P < 0.05). The factors significantly affecting patients' mental health were hormone dosage and disease activity index (DAI) (P < 0.05). The average optimism score of patients with SLE was 14.36 ± 4.42, and 30 cases were in the middle and lower levels. A positive correlation was found between optimism level and QoL scores. CONCLUSION: Patients with SLE develop psychological disorders at varying degrees, which are significantly influenced by hormone dosage and DAI. Patients' mental health should be closely monitored during clinical diagnosis and treatment and provided adequate support in establishing positive, healthy thinking and behavior patterns and improving their optimism level and QoL.
RESUMO
Dysregulated maturation and activation of dendritic cells (DCs) play a significant role in the progression of systemic lupus erythematosus (SLE). The autophagy-lysosome pathway has been identified as a potential mechanism to inhibit DC activation and maturation, but its precise workings remain unclear. We investigated the role and regulatory mechanism of TLR9 in modulating the autophagy-lysosome pathway and DCs activation. The mRNA and protein expressions were assessed using qRT-PCR and/or western blot. NZBW/F1 mice was used to construct a lupus nephritis (LN) model in vivo. Cell apoptosis was analyzed by TUNEL staining. Flow cytometry was adopted to analyze DCs surface markers. Lyso-tracker red staining was employed to analyze lysosome acidification. Levels of anti-dsDNA, cytokines, C3, C4, urine protein and urine creatinine were examined by ELISA. The results showed that TLR9 was markedly increased in SLE patients, and its expression was positively correlated with SLEDAI scores and dsDNA level. Conversely, TLR9 expression showed a negative correlation with C3 and C4 levels. Loss-of function experiments demonstrated that TLR9 depletion exerted a substantial inhibition of renal injury, inflammation, and DCs numbers. Additionally, upregulation of TLR9 promoted DCs maturation and activation through activation of autophagy and lysosome acidification. Further investigation revealed that TLR9 targeted TRAF6 to activate the cGAS-STING pathway. Rescue experiments revealed that inactivation of the cGAS/STING signaling pathway could reverse the promoting effects of TLR9 upregulation on DCs maturation, activation, and autophagy-lysosome pathway. Overall, our findings suggested that TLR9 activated the autophagy-lysosome pathway to promote DCs maturation and activation by activating TRAF6-cGAS-STING pathway, thereby promoting SLE progression.