| Title |
-
en
Close Association between Altered Urine-Urothelium Barrier and Tertiary Lymphoid Structure Formation in the Renal Pelvis during Nephritis
|
| Creator |
-
-
-
-
-
-
-
-
-
en
Ali, Elewa Yaser Hosny
-
|
| Accessrights |
open access |
| Subject |
-
Other
en
tertiary lymphoid structure
-
Other
en
renal pelvis
-
Other
en
urine
-
Other
en
urothelium
-
Other
en
nephritis
-
Other
en
chemokine
-
NDC
649
|
| Description |
-
Abstract
en
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.
|
| Publisher |
en
American Society of Nephrology
|
| Date |
|
| Language |
|
| Resource Type |
journal article |
| Version Type |
AM |
| Identifier |
HDL
http://hdl.handle.net/2115/87865
|
| Relation |
-
isVersionOf
DOI
https://doi.org/10.1681/ASN.2021040575
-
PMID
34686544
|
| Journal |
-
-
en
Journal of the American Society of Nephrology
-
Volume Number33
Issue Number1
Page Start88
Page End107
|
| File |
|
| Oaidate |
2023-07-26 |
