Podocyte-derived exosomes instruct dendritic cell-dependent CD8⁺ T cell activation and proliferation in renal inflammation.

Authors

Bin Qian, Shuya Mao, Yang Chen, Ying Liu, Mingchao Zhang, Dihan Zhu, Ke Zen, Yu Wang, Zhihong Liu, Limin Li

Published in

Journal of advanced research. Volume 88. Pages 885-898. Epub Jan 12, 2026.

Abstract

Minimal Change Disease (MCD) represents a prevalent pathological cause of nephrotic syndrome. While podocyte injury is recognized as the direct cause of proteinuria in MCD, aberrant T-cell activation is a key driver of this podocyte damage. However, the absence of T-cell infiltration in renal biopsies and ineffectiveness of immunosuppressive therapy in a subset of patients suggest the existence of undiscovered key mechanisms underlying MCD immunopathogenesis.
This study investigates the role of podocyte-derived exosomes (Pdo-Exos) in T cell activation via antigen presentation in MCD.
Using an in vitro co-culture system, a puromycin aminonucleoside (PAN)-induced MCD mouse model, and clinical samples, we evaluated the immunostimulatory capacity of Pdo-Exos, focusing on antigen presentation via MHC-I and Rab27a-regulated exosome secretion.
Pdo-Exos activated CD8⁺ T cells through MHC-I without promoting proliferation, indicating a role for dendritic cell-mediated cross-presentation. In OT-I mice, OVA-loaded Pdo-Exos exacerbated proteinuria and activated both tissue-resident and lymphoid T cells. MCD patients exhibited increased circulating activated T cells, and their podocyte exosomes showed significantly elevated MHC-I and co-stimulatory molecule CD80. Rab27a-dependent exosome secretion exacerbated disease severity, while inhibition of Rab27a mitigated proteinuria and inflammation.
Podocyte-derived exosomes mediate CD8⁺ T cell activation by acting as antigen-presenting vesicles, with DCs facilitating T cell expansion. Rab27a-dependent exosome secretion contributes to MCD progression, highlighting a novel therapeutic strategy.

PMID:
41534548
Bibliographic data and abstract were imported from PubMed on 14 Nov 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.