Heterogeneity and clinical relevance of tertiary lymphoid tissues in murine and human kidney

抄録

Background

Tertiary lymphoid tissues (TLTs) are inducible ectopic lymphoid tissue, which initiate adaptive immune responses and sustain inflammation. We previously demonstrated that aged but not young mice exhibited multiple TLTs after acute kidney injury, which correlated with inflammation and underlay maladaptive repair. TLTs were also detected in human aged and other diseased kidneys, yet the clinical relevance remains unclear because of the lack of methodology for their evaluation.

Methods

We analyzed human renal TLTs utilizing surgically resected kidneys from aged patients (N = 69) and pyelonephritis patients (N = 16) based on the results of TLT in murine model.

Results

TLTs in both groups shared a perivascular location as well as similar components, but exhibited heterogeneity in phenotype. We classified TLTs into three developmental stages based on their presumed developmental stages, and demonstrated in mouse that the stages advanced with the extent of kidney injury as well as with the time after kidney injury, and the stages were reversible with immunosuppressive agents. Consistently, the kidneys of aged patients with chronic kidney disease (CKD) exhibited more frequent and more advanced stages of TLTs than those without CKD.

Conclusion

We established the phenotypic evaluation method of TLT based on the presumed developmental stages and showed the potential of TLT stage as an inflammation marker in murine and human kidney. TLT staging strategy may be effective in assessing disease activity and efficacy of therapy, and therefore hold the potential to improve our assessment of CKD patients.