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

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

  • J Adv Res. 2026 Jan 12:S2090-1232(26)00057-3. doi: 10.1016/j.jare.2026.01.032.
Bin Qian 1,  Shuya Mao 2,  Yang Chen 3,  Ying Liu 4,  Mingchao Zhang 5,  Dihan Zhu 2,  Ke Zen 6,  Yu Wang 7,  Zhihong Liu 8,  Limin Li 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, Jiangsu 211198, China; National Clinical Research Center for Kidney Diseases, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210002, China.
  • 2 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, Jiangsu 211198, China.
  • 3 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, Jiangsu 211198, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009 China.
  • 4 Xuzhou Tongshan District Hospital of Traditional Chinese Medicine, Xuzhou, Jiangsu 221116, China.
  • 5 National Clinical Research Center for Kidney Diseases, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210002, China.
  • 6 State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, Nanjing University School of Life Sciences, Nanjing, Jiangsu 210046, China.
  • 7 Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, China. Electronic address: [email protected].
  • 8 National Clinical Research Center for Kidney Diseases, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210002, China. Electronic address: [email protected].
  • 9 State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Druggability of Biopharmaceuticals, School of Life Science and Technology, China Pharmaceutical University, 639 Longmian Avenue, Nanjing, Jiangsu 211198, China. Electronic address: [email protected].
PMID: 41534548 DOI: 10.1016/j.jare.2026.01.032
Abstract

Introduction: 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.

Objectives: This study investigates the role of podocyte-derived exosomes (Pdo-Exos) in T cell activation via antigen presentation in MCD.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords

Antigen presentation; Minimal change disease; Podocyte-derived exosomes; Rab27a; T cell activation.

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