Kidney Week

Abstract: TH-PO0405

Neonatal Fc Receptor in Glomerular Cells Promotes Proteinuria via Immune Complex-Triggered Inflammation in Imiquimod-Induced Lupus Model

Session Information

• Glomerular Diseases: Autoimmune Diseases
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology

Authors

• Nakano, Akihito, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan

Akihito Nakano, MD

• Maeda, Kayaho, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan

Kayaho Maeda, MD

• Sugiura, Takuya, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan

Takuya Sugiura, MD

• Shibata, Katsuaki, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan

Katsuaki Shibata, MD

• Sugimura, Masahiro, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan

Masahiro Sugimura, MD

• Kato, Noritoshi, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan

Noritoshi Kato, MD, PhD

• Kosugi, Tomoki, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan

Tomoki Kosugi, MD, PhD

• Maruyama, Shoichi, Nagoya Daigaku, Nagoya, Aichi Prefecture, Japan

Shoichi Maruyama, MD, PhD

Background

Lupus nephritis (LN) is a major organ manifestation of systemic lupus erythematosus, in which immune-complex (IC) deposition and inflammatory cell infiltration contribute to disease progression. We previously showed that IgG from patients with LN directly injures podocytes via a Ca²⁺/calmodulin-dependent kinase IV pathway, independent of immune cells. Podocyte uptake of IgG is mediated, at least in part, by the neonatal Fc receptor (FcRn), and FcRn inhibition reduces IgG internalization. We aim to investigate whether FcRn in glomerular cells initiates IgG-driven podocyte injury and to delineate FcRn-dependent mechanisms across glomerular cells, including mesangial cells.

Methods

We generated an imiquimod-induced lupus model in systemic FcRn-knockout (KO) and wild-type (WT) mice and compared renal phenotypes. Leukocyte subsets in kidney, spleen, and peripheral blood were analyzed by flow cytometry. We also created podocyte-specific FcRn-KO mice and performed similar evaluations. In vitro, primary mesangial cells isolated from systemic FcRn-KO and WT mice were stimulated with ICs prepared using sera from lupus-model mice or 4-hydroxy-3-nitrophenylacetyl-ovalbumin. Readouts included LN-relevant inflammatory mediators (e.g., cytokine production).

Results

In systemic FcRn-KO mice, imiquimod-induced proteinuria was attenuated versus WT. Serum IgG and anti-double-stranded DNA antibody levels were significantly lower in FcRn-KO mice. However, glomerular IgG and C3 deposition—predominantly mesangial—did not differ between groups. Spleen weight and leukocyte subset distributions in spleen and peripheral blood were comparable. These findings suggest that FcRn-dependent responses within glomerular resident cells to ICs, rather than systemic immune activation itself, drive proteinuria. In podocyte-specific FcRn-KO mice, proteinuria and histopathology were not different from controls. In vitro, IC stimulation of mesangial cells lacking FcRn resulted in reduced inflammatory cytokine expression compared with WT.

Conclusion

Systemic loss of FcRn mitigates proteinuria in an imiquimod-induced lupus model without altering glomerular IC deposition, implicating FcRn-mediated IC sensing within glomerular resident cells. Our data indicate that mesangial FcRn promotes pro-inflammatory cytokine production and contributes to LN progression.

Funding

• Government Support – Non-U.S.