Abstract: SA-PO397
Heterogeneity and Clinical Relevance of Tertiary Lymphoid Tissue in Murine and Human Kidneys
Session Information
- CKD: Risk Factors for Incidence and Progression - III
November 04, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Chronic Kidney Disease (Non-Dialysis)
- 301 CKD: Risk Factors for Incidence and Progression
Authors
- Sato, Yuki, Graduate School of Medicine, Kyoto University, Kyoto, Japan
- Boor, Peter, RWTH University of Aachen, Aachen, Germany
- Floege, Jürgen, RWTH University of Aachen, Aachen, Germany
- Yanagita, Motoko, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Background
Unlike reversible AKI in the young, AKI in the elderly often leads to end-stage renal disease. We previously demonstrated that after AKI aged but not young mice developed multiple renal tertiary lymphoid tissues (TLTs), which comprised mainly lymphocytes and fibroblasts. These promoted aberrant inflammation and underlied the “AKI to CKD sequence”. We also showed that aged ( > 60 yrs old) but not young (40 yrs old >) humans exhibited renal TLTs (Sato Y et al. JCI insight 2016). Although TLTs are closely involved in the pathophysiology of various chronic inflammatory diseases in human, the developmental stages and clinical relevance remain ill defined.
Methods
Utilizing surgically removed human kidney samples as well as the mouse TLT model, which we have recently established, we investigated the developmental stages and potential clinical relevance of renal TLTs. Human kidney samples were derived from 2 independent patient groups: Japanese aged patients and German pyelonephritis patients.
Results
Kidneys from patients with chronic pyelonephritis exhibited multiple heterogeneous TLTs, which appeared to represent various developmental stage of TLTs. The same cellular and molecular components such as CXCL13 and p75NTR in fibroblasts were detectable both in pyelonephritis-induced TLTs and age-dependent TLTs and proved indistinguishable, suggesting that TLT formation is a uniform response to injury irrespective of the etiology in human kidney. Furthermore, we classified TLTs into 3 groups based on their presumed developmental stages and found that the TLT-stage was closely associated with the severity of kidney injury in mice, raising the possibility that the presence and developmental stage of TLTs can be a predictor of kidney disease progression. In humans, the kidneys of aged patients with CKD exhibited more frequent and advanced TLT-stages than those without CKD, whereas in chronic pyelonephritic kidneys TLTs in advanced stages clustered in destroyed areas.
Conclusion
TLT-formation in murine and human kidneys appears to be a relatively uniform process that proceeds through several stages. Stratification using the TLT-stages may offer a novel strategy to evaluate the CKD patients and potentially improve their therapeutic approaches.
Funding
- Commercial Support – Mitsubishi tanabe pharma corporation