Cordyceps Protein Helps Kidney Health by Reducing Immune Cell Activity in Lupus

Greg Howard
30th June, 2024

Cordyceps Protein Helps Kidney Health by Reducing Immune Cell Activity in Lupus

Image Source: Natural Science News, 2024

Key Findings

  • Researchers at Chengdu University found that a protein from cordyceps (WCP) significantly improved lupus nephritis (LN) symptoms in mice
  • WCP treatment reduced urinary protein, creatinine, and serum autoantibodies, while increasing immune-boosting complement 3 (C3) levels
  • The study showed that WCP decreased harmful T cell infiltration in the kidneys and inhibited inflammatory pathways, offering a new potential treatment for LN
Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE), an autoimmune disease where the body's immune system attacks its own tissues, particularly the kidneys. LN affects up to 60% of patients with SLE and is a significant cause of morbidity and mortality[2][3][4]. Despite advancements in understanding the disease's pathogenesis and treatment options, LN remains a challenging condition to manage, with a high risk of kidney failure[3]. Traditional treatments often involve immunosuppressive therapies, which carry various side effects and are not always effective[2]. Recent research conducted by Chengdu University of Traditional Chinese Medicine has explored the potential of a protein derived from cordyceps (WCP), a traditional Chinese medicine, in treating LN[1]. The study aimed to assess the immunomodulatory effects of WCP in LN mice and to elucidate the underlying mechanisms through both in vivo (within a living organism) and in vitro (outside a living organism) investigations. The researchers used MRL/lpr lupus-prone mice, a common animal model for studying LN. They administered WCP (1.5 g/kg/day), Bailing capsules (BC, 0.75 g/kg/day), and saline to the mice over eight weeks. The therapeutic effects of WCP were evaluated using various techniques, including ELISA (a test that measures antibody levels in the blood), Hematoxylin-eosin (H&E) and Periodic Acid Schiff (PAS) staining (methods for examining tissue samples), immunofluorescence, Luminex analysis, and flow cytometry. To understand the mechanism by which WCP alleviates LN, the researchers used transcriptomics, Western blot (WB), and Real-time quantitative polymerase chain reaction (RT-qPCR) on tissues, T cells, and Mouse Podocyte Clone-5 (MPC-5) cells. The results showed that WCP significantly improved LN symptoms in MRL/lpr mice. Specifically, WCP reduced urinary protein, creatinine, and serum autoantibodies, while increasing complement 3 (C3) levels, which are crucial for immune function. The treatment also improved renal immunopathology and downregulated serum cytokines, including IFN-γ, IL-12, and RANTES, which are involved in inflammatory responses. A notable finding was the reduction in the infiltration of CD4+ and CD8+ T cells in the kidneys of WCP-treated mice. T cells play a central role in the development and progression of LN by infiltrating the kidneys and causing inflammation and damage. This aligns with previous studies highlighting the significance of T cell infiltration and differentiation in LN[2][3]. The cell transwell co-culturation study further confirmed that WCP-treated MPC-5 cells were less effective in inducing T cell migration, indicating a direct impact on T cell behavior. The study also revealed that WCP could inhibit T cell-related chemokine expression in kidney and MPC-5 cells. Chemokines are signaling proteins that attract immune cells to sites of inflammation. Additionally, WCP reduced the levels of TLR4, MYD88, phosphorylated-p38, phosphorylated-ERK, and phosphorylated-JNK, indicating that WCP affects the TLR4/MYD88/MAPK signaling pathway, which is involved in immune responses. Moreover, WCP was found to inhibit Th1 cell differentiation both in vivo and in vitro. Th1 cells are a subset of T cells that produce inflammatory cytokines like IFN-γ and play a crucial role in autoimmune diseases. The researchers identified that the cytokine-receptor induced Th1 cell differentiation pathway and the PI3K-AKT pathway were the most enriched pathways based on differentially expressed genes (DEGs) enrichment analysis among different cell groups. RT-qPCR and WB results showed that WCP notably reduced the levels of IL-12, p-STAT4, IFN-γ, p-STAT1, p-PI3K, and p-AKT in T cells, further elucidating the molecular mechanisms behind WCP's effects. In conclusion, the study by Chengdu University of Traditional Chinese Medicine demonstrated that WCP has positive immunomodulatory effects on LN by decreasing T cell infiltration through the TLR4/MYD88/MAPK signaling pathway and inhibiting Th1 cell differentiation via the IL-12-STAT4 and IFN-γ-STAT1 pathways, as well as the PI3K-AKT pathway. These findings offer promising insights into new therapeutic strategies for LN, addressing some of the deficiencies in current treatment approaches highlighted in previous studies[2][3][4].

MedicineBiochemMycology

References

Main Study

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

Published 28th June, 2024

https://doi.org/10.1016/j.intimp.2024.112566

Related Studies

3) Update on Lupus Nephritis: Core Curriculum 2020.

https://doi.org/10.1053/j.ajkd.2019.10.017

4) Advances in Lupus Nephritis Pathogenesis: From Bench to Bedside.

https://doi.org/10.3390/ijms22073766


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