CMPK2 promotes CD4+T cell pyroptosis via NLRP3 in systemic lupus erythematosus
10.19405/j.cnki.issn1000-1492.2024.12.021
- Author:
Yanan Tan
1
,
2
;
Gege Jiang
1
,
2
;
Li Jin
3
;
Nan Xiang
3
;
Xiaoge Sun
3
;
Xiaoyi Jia
4
;
Min Zhang
3
Author Information
1. School of Pharmacy , Anhui University of Traditional Chinese Medicine , Hefei 230012
2. The First Afiliated Hospital of USTC (Anhui Provincial Hospital) , Hefei 230001
3. The First Afiliated Hospital of USTC (Anhui Provincial Hospital) , Hefei 230001
4. School of Pharmacy , Anhui University of Traditional Chinese Medicine , Hefei 230012
- Publication Type:Journal Article
- Keywords:
systemic lupus erythematosus;
CD4 + T cell;
CMPK2;
biomarker;
NLRP3;
pyroptosis
- From:
Acta Universitatis Medicinalis Anhui
2024;59(12):2215-2221
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the levels of cytidine/uridine monophosphate kinase 2(CMPK2) expression in CD4+T cells of systemic lupus erythematosus(SLE) patients and its correlation with clinical indicators. Additionally, to explore whether CMPK2 can induce pyroptosis in CD4+T cells of SLE patients through NLRP3, potentially providing a new target for the diagnosis and treatment of SLE.
Methods:RT-qPCR and Western blot analyses were used to assess the gene and protein expression levels of CMPK2 in SLE CD4+T cells and healthy controls(HC). Pearson or Spearman correlation analysis was performed to evaluate the relationship between CMPK2 mRNA expression levels and clinical indicators. Subsequently, the expression levels of pyroptosis-related proteins, including NLRP3, apoptosis-associated speck-like protein containing a CARD(ASC), caspase-1, gasdermin D(GSDMD), and the N-terminal domain of GSDMD(GSDMD-N), were examined in SLE CD4+T cells and HC. Furthermore, the protein expression levels of NLRP3, ASC, caspase-1, GSDMD, and GSDMD-N were detected after silencingCMPK2in SLE CD4+T cells.
Results:CMPK2 expression was significantly elevated in SLE CD4+T cells, exhibiting a positive correlation with SLE disease activity index(SLEDAI), anti-dsDNA antibody, anti-nucleosome antibody, anti-C1q antibody, and a negative correlation with complement C3 and C4 levels. Additionally, the expression levels of pyroptosis-related proteins, including NLRP3, ASC, caspase-1, GSDMD, and GSDMD-N significantly increased in SLE CD4+T cells(P<0.05), Moreover, the levels of cytokines IL-1β and IL-18 in the cell culture supernatants were elevated, and there was a notable increase in the rate of cellular pyroptosis(P<0.05). Silencing CMPK2 led to a reduction in the levels of these markers(P<0.05).
Conclusion:CMPK2 is highly expressed in SLE CD4+T cells and may serve as a diagnostic marker for SLE. Moreover, it is likely involved in the pathogenesis of SLE by promoting CD4+T cell pyroptosis through NLRP3.
- Full text:2025022809065685696CMPK2通过NLRP3促...患者CD4~+_T细胞焦亡_谭亚楠.pdf
