Kidney Week

Abstract: TH-PO0221

B Cell-Intrinsic Toll-Like Receptor 7 Signaling Drives Tertiary Lymphoid Structures Formation in Injured Kidneys

Session Information

• CKD: Mechanisms of Injury and Fibrosis - 1
  October 22, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 2203 CKD (Non-Dialysis): Mechanisms

Authors

• Goto, Shima, Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

Shima Goto, DVM

• Yoshikawa, Takahisa, Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

Takahisa Yoshikawa, MD, PhD

• Toriu, Naoya, Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

Naoya Toriu, MD

• Taniguchi, Keisuke, Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

Keisuke Taniguchi, MD

• Sato, Yuki, Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

Yuki Sato, MD, PhD

• Hattori, Masakazu, Laboratory of Tumor Tissue Response, Graduate School of Medicine, Kyoto University, Kyoto, Japan

Masakazu Hattori, PhD, DVM

• Yanagita, Motoko, Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

Motoko Yanagita, MD, PhD

Background

Tertiary lymphoid structures (TLS) are organized ectopic lymphoid aggregates and form in aged injured kidneys and in human CKD, and are associated with poor prognosis. Interaction between senescence-associated T (SA-T) cells and age-associated B cells (ABCs) drives TLS expansion, and both lymphocytes are induced by aging and toll-like receptor 7 (TLR7) signaling. However, whether TLR7 signaling directly promotes TLS formation remains unclear.

Methods

We evaluated cell-types expressing TLR7 and TLS formation in injured kidneys after ischemia-reperfusion injury (IRI) using aged Tlr7 knockout (KO) mice, aged C57BL/6J (B6J) mice treated with TLR7 inhibitors, young B6J mice treated with TLR7 agonists, and B cell-specific Tlr7 KO mice generated by bone marrow transplantation. Additionally, TLR7-expressing cells were also analyzed in human kidneys with TLS, and public RNA-seq dataset of human CKD were also reanalyzed.

Results

TLR7 was expressed in B cells, macrophages, and dendritic cells in aged injured kidneys with TLS. In aged Tlr7 KO mice and TLR7 inhibitor-treated mice, renal TLS expansion and maturation were suppressed, accompanied by the reduction of ABCs and SA-T cells. In young mice post-IRI, the administration of TLR7 agonist was sufficient to recapitulate mature TLS formation in aged injured kidneys, accompanied by increased ABCs and SA-T cells. In mice with B cell-specific TLR7 deficiency, TLS formation was significantly reduced, indicating that TLR7 in B cells was essential for TLS expansion. Furthermore, TLR7-expressing B cells were detected within TLS in human kidneys. Reanalysis of public RNA-seq data of human CKD kidneys showed that TLR7 expression positively correlated with TLS-associated gene expression and negatively correlated with eGFR.

Conclusion

TLR7 signaling, especially in B cells, is both necessary and sufficient for renal TLS formation. Moreover, its negative correlation with kidney dysfunction in human CKD suggests an important role in CKD progression. These findings contribute to the further understanding of molecular mechanisms underlying TLS formation in kidneys, leading to development of therapeutic approaches for CKD with TLS.