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Abstract: TH-PO974

Tertiary Lymphoid Tissue Is a Novel Histological Marker Reflecting Local Injury and Inflammation in Murine and Human Kidneys

Session Information

Category: Pathology and Lab Medicine

  • 1501 Pathology and Lab Medicine: Basic

Authors

  • Sato, Yuki, Kyoto University Graduate School of Medicine, Kyoto, KYOTO, Japan
  • Boor, Peter, RWTH University of Aachen, Aachen, Germany
  • Floege, Jürgen, RWTH University of Aachen, Aachen, Germany
  • Yanagita, Motoko, Department of Nephrology, Kyoto University Graduate School of Medicine, Kyoto, Japan
Background

Tertiary lymphoid tissues (TLTs) are ectopic lymphoid tissues that are formed under various pathologic conditions such as autoimmunity and infection, and support priming of immune responses. We previously demonstrated that aged but not young mice exhibited multiple TLTs after AKI, which underlie maladaptive repair. TLTs were also detected in human aged and diseased kidneys, yet the comprehensive understanding is lacking and the clinical relevance remains controversial.

Methods

We analyzed human renal TLTs utilizing surgically resected kidneys from aged patients (N=69) and pyelonephritis patients (N=16) and proposed a novel staging scheme of TLTs. To validate this, we utilized murine TLT model utilizing aged mice subject to IRI. In this model, TLTs develop and expand as ischemic time or the time after IRI increase.

Results

TLTs in both human groups shared a perivascular, periglomerular and subcapsular location as well as similar components such as a homeostatic chemokine CXCL13, but exhibited heterogeneity in phenotype. We classified TLTs into three developmental stages based on the presence of follicular dendritic cells and germinal centers, and demonstrated in mice that the TLT stages advanced with the extent of kidney injury. Dexamethasone treatment after TLT formation decreased the size of TLTs, accompanied with improvement of renal inflammation and fibrosis, indicating the reversibility of TLTs. Consistently, the kidneys of aged patients with CKD exhibited more frequent and more advanced stages of TLTs than those without CKD, and pyelonephritis kidneys exhibited more frequent TLTs with more advanced stages than aged CKD kidneys.

Conclusion

Spatial and developmental similarities of TLTs in both groups indicated that TLT formation might not be disease-specific but rather a common pathological process. On the other hand, the phenotypic heterogeneity of TLTs reflected severity of kidney injuries, which explained the high frequency and advanced stages of TLTs in the kidneys with severe pyelonephritis. The reversibility of TLTs also indicated the potential of TLT-associated molecules as a novel candidate of biomarkers reflecting renal injury. Taken together, our data provide a mechanistic framework for studying TLT formation as a previously unappreciated pathological pathway in kidney disease progression in mouse and human.

Funding

  • Private Foundation Support