Cordyceps protein alleviates renal injury by inhibiting T cell infiltration and Th1 cell differentiation in lupus nephritis mice.

Autor: Liao Z; College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China; Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, Chengdu, PR China., Yang X; State Key Laboratory of Southwestern Chinese Medicine Resources, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China., He L; State Key Laboratory of Southwestern Chinese Medicine Resources, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China., Bai J; College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China; Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, Chengdu, PR China., Zhou X; State Key Laboratory of Southwestern Chinese Medicine Resources, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China., Yang J; College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China; Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, Chengdu, PR China., Niu S; College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China; Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, Chengdu, PR China., Liu S; College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China; Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, Chengdu, PR China. Electronic address: liusijing@cdutcm.edu.cn., Guo J; College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China; Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine, Chengdu, PR China; State Key Laboratory of Southwestern Chinese Medicine Resources, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, PR China. Electronic address: guo596@cdutcm.edu.cn.
Jazyk: angličtina
Zdroj: International immunopharmacology [Int Immunopharmacol] 2024 Sep 10; Vol. 138, pp. 112566. Date of Electronic Publication: 2024 Jun 28.
DOI: 10.1016/j.intimp.2024.112566
Abstrakt: Background: T cell infiltration and differentiation play a central part in the development of lupus nephritis (LN). Our prior research has indicated that protein, the primary active component of cordyceps (WCP), a traditional Chinese medicine, possesses properties that can enhance renal fibrosis and provide kidney protection. Nonetheless, the connection between WCP and T cell infiltration and differentiation in LN remains poorly understood.
Objective: The objective of this research was to assess the immunomodulatory impacts of WCP in LN mice and elucidate the underlying mechanism through in vivo and in vitro investigations.
Methods: To investigate the impact and mechanism of WCP in MRL/lpr lupus-prone mice, WCP (1.5 g/kg/d), Bailing capsules (BC, 0.75 g/kg/d), and saline in equivalent quantities were administered to the mice over a period of 8 weeks. The therapeutic effects, T cell infiltration and differentiation of WCP on MRL/lpr mice were verified through ELISA, Hematoxylin-eosin (H&E), Periodic Acid Schiff (PAS) staining, immunofluorescence, Luminex analysis and flow cytometry. The mechanism by which WCP alleviates LN was investigated using tissues of mice, T cells and Mouse Podocyte Clone-5 (MPC-5) cells by transcriptomics, Western blot (WB), and Real-time quantitative polymerase chain reaction (RT-qPCR).
Results: We found that WCP improved LN in MRL/lpr mice by reducing urinary protein, creatinine, and serum auto antibodies, increasing complement 3 (C3) level, improving renal immunopathology and downregulating serum cytokines, including IFN-γ, IL-12, and RANTES. Notably, the infiltration of CD4 + and CD8 + T cells in the kidney was reduced by WCP. Similarly, the cell transwell co-culturation study showed that the WCP treated MPC-5 cells were weaker in inducing T cell migration. Consistent with this finding, our observations revealed that WCP could inhibit T cell-related chemokine expression in kidney and MPC-5 cells, as well as reduce the levels of TLR4, MYD88, phosphorylated-p38, phosphorylated-ERK, and phosphorylated-JNK. On the other hand, WCP was found to greatly inhibit the Th1 cells differentiation in vivo and in vitro. Cytokine-receptor induced Th1 cell differentiation pathway and PI3K-AKT pathway were the most enriched pathways based on differentially expressed genes (DEGs) enrichment analysis among different cell groups. Results from RT-qPCR and WB showed that WCP notably reduced the levels of IL-12, p-STAT4, IFN-γ, p-STAT1, p-PI3K, and p-AKT in T cells.
Conclusion: WCP demonstrated positive immunomodulatory effects on LN disease, by decreasing the T cells infiltration through TLR4/MYD88/MAPK signaling pathway and inhibiting Th1 cells differentiation via IL-12-STAT4 and IFN-γ-STAT1 pathways, in addition to the PI3K-AKT pathway.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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