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

Ichii, Osamu; Hosotani, Marina; Masum, Md. Abdul; Horino, Taro; Otani, Yuki; Namba, Takashi; Nakamura, Teppei; Ali, Elewa Yaser Hosny; Kon, Yasuhiro

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

Ichii, Osamu; Hosotani, Marina; Masum, Md. Abdul et al.

Journal of the American Society of Nephrology, 2022, 33(1), 88-107

Permalink : https://hdl.handle.net/2115/87865

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アクセス権	open access
URI	https://hdl.handle.net/2115/87865
タイトル	Close Association between Altered Urine-Urothelium Barrier and Tertiary Lymphoid Structure Formation in the Renal Pelvis during Nephritis
著者	Ichii, Osamu ; Hosotani, Marina ; Masum, Md. Abdul ; Horino, Taro ; Otani, Yuki ; Namba, Takashi ; Nakamura, Teppei ; Ali, Elewa Yaser Hosny ; Kon, Yasuhiro
e-Rad_Researcher 60547769 著者名 Ichii, Osamu
著者名 Hosotani, Marina
著者名 Masum, Md. Abdul
著者名 Horino, Taro
著者名 Otani, Yuki
著者名 Namba, Takashi
e-Rad_Researcher 80786773 著者名 Nakamura, Teppei
著者名 Ali, Elewa Yaser Hosny
e-Rad_Researcher 10178402 著者名 Kon, Yasuhiro
言語	英語
キーワード	tertiary lymphoid structure
	renal pelvis
	urine
	urothelium
	nephritis
	chemokine
発行日	2022-01
出版者	American Society of Nephrology
収録物名	Journal of the American Society of Nephrology
巻(号)	33(1)
ページ	88-107
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Accepted Manuscript
PISSN	1046-6673
関連情報	PMID 34686544
関連情報 (isVersionOf)	出版社版DOI https://doi.org/10.1681/ASN.2021040575