HUSCAP logo Hokkaido Univ. logo

Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine >
Peer-reviewed Journal Articles, etc >

Close Association between Altered Urine-Urothelium Barrier and Tertiary Lymphoid Structure Formation in the Renal Pelvis during Nephritis

Files in This Item:
Manuscript_20230201.pdf18.25 MBPDFView/Open
Please use this identifier to cite or link to this item:

Title: Close Association between Altered Urine-Urothelium Barrier and Tertiary Lymphoid Structure Formation in the Renal Pelvis during Nephritis
Authors: Ichii, Osamu Browse this author →KAKEN DB
Hosotani, Marina Browse this author
Masum, Md. Abdul Browse this author
Horino, Taro Browse this author
Otani, Yuki Browse this author
Namba, Takashi Browse this author
Nakamura, Teppei Browse this author →KAKEN DB
Ali, Elewa Yaser Hosny Browse this author
Kon, Yasuhiro Browse this author →KAKEN DB
Keywords: tertiary lymphoid structure
renal pelvis
Issue Date: Jan-2022
Publisher: American Society of Nephrology
Journal Title: Journal of the American Society of Nephrology
Volume: 33
Issue: 1
Start Page: 88
End Page: 107
Publisher DOI: 10.1681/ASN.2021040575
PMID: 34686544
Abstract: Background Kidneys with chronic inflammation develop tertiary lymphoid structures (TLSs). Infectious pyelonephritis is characterized by renal pelvis (RP) inflammation. However, the pathologic features of TLSs, including their formation and association with non-infectious nephritis, are unclear. Methods RPs from humans and mice that were healthy or had non-infectious chronic nephritis were analyzed for TLS development, and the mechanism of TLS formation investigated using urothelium or lymphoid structure cultures. Results Regardless of infection, TLSs in the RP, termed urinary tract-associated lymphoid structures (UTALSs), formed in humans and mice with chronic nephritis. Moreover, urine played a unique role in UTALS formation. Specifically, we identified urinary IFN-gamma as a candidate factor affecting urothelial barrier integrity because it alters occludin expression. In a nephritis mouse model, urine leaked from the lumen of the RP into the parenchyma. In addition, urine immunologically stimulated UTALS-forming cells via cytokine (IFN-gamma, TNF-alpha) and chemokine (CXCL9, CXCL13) production. CXCL9 and CXCL13 were expressed in UTALS stromal cells and urine stimulation specifically induced CXCL13 in cultured fibroblasts. Characteristically, type XVII collagen (BP180), a candidate autoantigen of bullous pemphigoid, was ectopically localized in the urothelium covering UTALSs and associated with UTALS development by stimulating CXCL9 or IL-22 induction via the TNF-alpha/ FOS/JUN pathway. Notably, UTALS development indices were positively correlated with chronic nephritis development. Conclusions TLS formation in the RP is possible and altered urine-urothelium barrier-based UTALS formation may represent a novel mechanism underlying the pathogenesis of chronic nephritis, regardless of urinary tract infection.
Type: article (author version)
Appears in Collections:獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 市居 修

Export metadata:

OAI-PMH ( junii2 , jpcoar_1.0 )

MathJax is now OFF:


 - Hokkaido University