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Kidney Week

Abstract: SA-OR56

CD153-CD30 Signaling Is Required for Age-Dependent Tertiary Lymphoid Tissue Expansion in the Kidney

Session Information

Category: CKD (Non-Dialysis)

  • 2103 CKD (Non-Dialysis): Mechanisms

Authors

  • Sato, Yuki, Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  • Oguchi, Akiko, Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  • Toriu, Naoya, Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  • Taniguchi, Keisuke, Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  • Yoshikawa, Takahisa, Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  • Hosoi, Takeshi, MIC TMKP, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  • Kondo, Makiko, Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  • Komidori, Shota, Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
  • Boor, Peter, Institute of Pathology, RWTH University of Aachen, Aachen, Germany
  • Floege, Jürgen, Department of Nephrology, RWTH University of Aachen, Aachen, Germany
  • Yanagita, Motoko, Department of Nephrology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Background

The elderly show a reduced capacity for renal regeneration after acute kidney injury (AKI). We previously showed that, after AKI, aged, but not young, kidneys exhibit tertiary lymphoid tissues (TLTs), which underlie maladaptive repair in aged injured kidneys. TLTs facilitate lymphocyte activation and differentiation in situ and are involved in pathophysiology in various diseases. However, the cells and signals responsible for age-dependent TLT formation in the kidneys are still undefined.

Methods

We investigated immune cells in aged injured kidneys with TLTs, 45 days after ischemic reperfusion injury, utilizing scRNAseq and bulk RNAseq, combined with flow cytometry and reporter mouse analysis. We also investigated human kidney samples harboring TLTs.

Results

We observed accumulation of CD153+PD-1+CD4+ senescence-associated T (SAT) cells and CD30+T-bet+ age-associated B cells (ABCs), within TLTs in aged kidneys. Both SAT cells and ABCs are unique age-dependent lymphocyte populations and have been demonstrated to contribute to the pathophysiology of autoimmune diseases and obesity. By scRNAseq, SAT cells were further divided into two subpopulations, peripheral helper-like T cells and IL10-producing T cells, both of which are specialized CD4+ T cell subpopulations with B cell helper functions. CD153 and CD30 were specifically expressed in SAT cells and ABCs, respectively, and their expression was confined within TLTs in aged injured kidneys. In kidney injury models, CD153 or CD30 deficiency reduced ABC numbers, resulting in attenuated TLT formation with less inflammation and fibrosis and better renal function. Mechanistically, SAT cells from CD30-deficient mice exhibited decreased expression of Il21 and Il10, indicating CD153-CD30 signaling was required for SAT cells to acquire B cell helper functions. CD153-expressing cells were detected within TLTs in human kidneys, and human Tph/TFH-like cells and ABCs in chronically inflammatory organs also expressed CD153 and CD30, respectively.

Conclusion

These findings identify CD153-CD30 signaling between SAT cells and ABCs as a pivotal regulator of age-dependent TLT formation and suggest that targeting CD153-CD30 signal may be a valuable strategy for the prevention and treatment of kidney diseases in the elderly.

Funding

  • Government Support – Non-U.S.