Related Experiment Video

Updated: Jan 30, 2026

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
07:15

Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway

Published on: August 23, 2024

943

V-domain immunoglobulin suppressor of T-cell activation regulates CD4+ T cell activation and podocyte function

Zhijie Luo1, Qiqi Zhang1, Tingting Zhang1

  • 1New Drug Screening and Pharmacodynamics Evaluation Center, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.

Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie
|January 28, 2026
PubMed

The activation of V-domain immunoglobulin suppressor of T-cell activation (VISTA) has shown its therapeutic potential in murine lupus-like disease through immunoregulation, particularly suppressing CD4+ T cell activation. Podocytes are critical for preventing proteinuria in lupus nephritis (LN). However, the mechanisms by which VISTA regulate CD4+ T cells and renal podocytes remain unclear. Here, we demonstrated that CD4+ T cells from VISTA knockout mice showed upregulated phosphorylation of PI3K/AKT, increased secretion of IFN-γ, IL-17 and CD40L. Soluble VISTA mitigated inflammation and recovered the expression of structural proteins Podocin through inhibition of PI3K/AKT/mTOR signaling pathway and induction of autophagy. Moreover, previously demonstrated VISTA agonist Baloxavir marboxil decreased renal CD4+ T cells, restored the expression of Nephrin and Podocin, and promoted autophagy. Our study suggests that VISTA plays an important role in the pathogenesis of LN, which offers novel mechanisms and potential target for its application in LN therapy.

Keywords:
CD4(+)T cellsLupus nephritisPI3K/AKT signaling pathwayPodocytesVISTA

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