Kidney Week

Abstract: TH-PO0414

PU.1-Positive Cells in Lupus Nephritis-Like Mouse Glomeruli and Human Lupus Nephritis Biopsies Support SPI1/PU.1 as a Candidate Marker and Regulator

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

• Takahashi, Yusuke, Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University Graduate School of Medicine, Dentistry and Health Sciences, Niigata, Japan

Yusuke Takahashi, MD

• Isozaki, Shunsuke, Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University Graduate School of Medicine, Dentistry and Health Sciences, Niigata, Japan

Shunsuke Isozaki, MD

• Takahashi, Megumi, Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University Graduate School of Medicine, Dentistry and Health Sciences, Niigata, Japan

Megumi Takahashi, MD

• Watanabe, Hirofumi, Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University Graduate School of Medicine, Dentistry and Health Sciences, Niigata, Japan

Hirofumi Watanabe, MD, PhD

• Otsuka, Tadashi, Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University Graduate School of Medicine, Dentistry and Health Sciences, Niigata, Japan

Tadashi Otsuka, MD, PhD

• Yamamoto, Suguru, Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University Graduate School of Medicine, Dentistry and Health Sciences, Niigata, Japan

Suguru Yamamoto, MD, PhD

Background

MRL/lpr mice are an autoimmune-prone model with an interferon-biased immune background relevant to lupus nephritis (LN). LPS, a TLR4 ligand, triggers innate immune activation, but the glomerular transcriptional and immune-cell responses to acute LPS challenge, and their relevance to human LN tissue, remain incompletely defined.

Methods

MRL/lpr mice received a single intraperitoneal injection of LPS or PBS, and kidneys were harvested 24 h later (n=4/group). Kidney sections were assessed by histology and immunostaining for CD44, F4/80, and PU.1. Glomeruli were analyzed by qPCR and bulk RNA-seq with transcription factor activity inference. Dual F4/80 and PU.1 immunostaining was performed to evaluate overlap with macrophage-lineage cells. Public PBMC single-cell RNA-seq data were analyzed to assess SPI1 expression in human LN monocytes. For human tissue validation, LN biopsy specimens were collected from our institutional renal biopsy registry, classified according to the ISN/RPS classification, and subjected to PU.1 immunostaining.

Results

LPS increased glomerular injury, CD44-positive glomeruli, F4/80-positive macrophage infiltration, and expression of inflammatory cytokines and CD45. RNA-seq identified SPI1 as the top activated regulator among LPS-upregulated genes. Public single-cell RNA-seq showed higher SPI1 expression in LN monocytes than in healthy controls. PU.1-positive intraglomerular cells were rare in PBS controls but were observed in LPS-induced LN-like glomeruli. Dual immunostaining showed partial, rather than complete, overlap between PU.1-positive cells and F4/80-positive macrophage-lineage cells. PU.1-positive intrarenal cells were detected in ISN/RPS-classified human LN biopsy specimens.

Conclusion

These findings connect transcriptomic SPI1 activation with histologic detection of PU.1-positive cells in LN-like mouse glomeruli and human LN tissue, supporting SPI1/PU.1 as a candidate marker and regulator in LN.

Funding

• Government Support – Non-U.S.