Tertiary lymphoid tissues in kidney diseases: a perspective for the pediatric nephrologist.

Chronic kidney disease (CKD) is a major public health problem worldwide. In the pediatric population, CKD is also an important health issue because it causes several comorbid conditions that can have long-term consequences beyond the pediatric age. Chronic inflammation is a common pathological feature of CKD, irrespective of etiology, and leads to maladaptive repair and kidney dysfunction. Tertiary lymphoid tissues (TLTs) are ectopic lymphoid structures that develop in non-lymphoid organs under chronic inflammation caused by pathological conditions, including infections, autoimmune diseases, and cancers. TLTs in the kidneys have been poorly researched due to the lack of an animal model. We have recently found that, in aged but not young mice, TLTs develop in multiple kidney injury models, and the analysis of age-dependent TLTs has brought about several novel insights into the development and pathogenic impacts of TLTs in the kidney. Age-dependent TLT formation is also observed in human kidneys. In addition to aged kidneys, TLT development is also reported in several human kidney diseases including kidney allografts, lupus nephritis, and IgA nephropathy in both adults and children. In this review, we describe the novel findings on TLTs in the kidney obtained mainly from the analysis of age-dependent TLTs and discuss the clinical relevance of TLTs in kidney diseases.