HBx promotes glomerular podocyte-induced immune cell responses.
Ren Fail
; 46(2): 2373276, 2024 Dec.
Article
in En
| MEDLINE
| ID: mdl-38967134
ABSTRACT
BACKGROUND:
Podocytes, as intrinsic renal cells, can also express MHC-II and costimulatory molecules under inflammatory conditions, suggesting that they may act as antigen-presenting cells (APCs) to activate immune cell responses and then lead to immune-mediated renal injury. They are already recognized as main targets in the pathogenic mechanism of hepatitis B virus (HBV)-associated glomerulonephritis (HBV-GN). Previous studies also have indicated that inflammatory cells infiltration and immune-mediated tissue injury are evident in the kidney samples of patients with HBV-GN. However, the role of podocytes immune disorder in the pathogenic mechanism of HBV-GN remains unclear.METHODS:
Renal function and inflammatory cells infiltration were measured in HBV transgenic (HBV-Tg) mice. In vitro, podocytes/CD4+ T cells or macrophages co-culture system was established. Then, the expression of HBx, CD4, and CD68 was determined by immunohistochemistry, while the expression of MHC-II, CD40, and CD40L was determined by immunofluorescence. Co-stimulatory molecules expression was examined by flow cytometry. The levels of inflammatory factors were detected by ELISA.RESULTS:
In vivo, renal function was obviously impaired in HBV-Tg mice. HBx was significantly upregulated and immune cells infiltrated in the glomerulus of HBV-Tg mice. Expression of MHC-II and costimulatory molecule CD40 increased in the podocytes of HBV-Tg mice; CD4+ T cells exhibited increased CD40L expression in glomerulus. In vitro, CD40 expression was markedly elevated in HBx-podocytes. In co-culture systems, HBx-podocytes stimulated CD4+ T cells activation and caused the imbalance between IFN-γ and IL-4. HBx-podocytes also enhanced the adhesion ability of macrophages and induced the release of proinflammatory mediators.CONCLUSION:
Taken together, these podocyte-related immune disorder may be involved in the pathogenic mechanism of HBV-GN.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Mice, Transgenic
/
Trans-Activators
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Hepatitis B virus
/
Podocytes
/
Viral Regulatory and Accessory Proteins
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Glomerulonephritis
Limits:
Animals
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Humans
/
Male
Language:
En
Journal:
Ren Fail
Journal subject:
NEFROLOGIA
Year:
2024
Document type:
Article
Affiliation country:
Country of publication: