Skip to main content

Main menu

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • JASN Podcasts
    • Article Collections
    • Archives
    • Kidney Week Abstracts
    • Saved Searches
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Editorial Team
  • Editorial Fellowship
    • Editorial Fellowship Team
    • Editorial Fellowship Application Process
  • More
    • About JASN
    • Advertising
    • Alerts
    • Feedback
    • Impact Factor
    • Reprints
    • Subscriptions
  • ASN Kidney News
  • Other
    • ASN Publications
    • CJASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology

User menu

  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
American Society of Nephrology
  • Other
    • ASN Publications
    • CJASN
    • Kidney360
    • Kidney News Online
    • American Society of Nephrology
  • Subscribe
  • My alerts
  • Log in
  • My Cart
Advertisement
American Society of Nephrology

Advanced Search

  • Home
  • Content
    • Published Ahead of Print
    • Current Issue
    • JASN Podcasts
    • Article Collections
    • Archives
    • Kidney Week Abstracts
    • Saved Searches
  • Authors
    • Submit a Manuscript
    • Author Resources
  • Editorial Team
  • Editorial Fellowship
    • Editorial Fellowship Team
    • Editorial Fellowship Application Process
  • More
    • About JASN
    • Advertising
    • Alerts
    • Feedback
    • Impact Factor
    • Reprints
    • Subscriptions
  • ASN Kidney News
  • Follow JASN on Twitter
  • Visit ASN on Facebook
  • Follow JASN on RSS
  • Community Forum
Basic Research
You have accessRestricted Access

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

Osamu Ichii, Marina Hosotani, Md. Abdul Masum, Taro Horino, Yuki Otani, Takashi Namba, Teppei Nakamura, Elewa Yaser Hosny Ali and Yasuhiro Kon
JASN January 2022, 33 (1) 88-107; DOI: https://doi.org/10.1681/ASN.2021040575
Osamu Ichii
1Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan
2Laboratory of Agrobiomedical Science, Faculty of Agriculture, Hokkaido University, Sapporo, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Osamu Ichii
Marina Hosotani
3Laboratory of Anatomy, School of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Marina Hosotani
Md. Abdul Masum
1Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan
4Department of Anatomy, Histology and Physiology, Faculty of Animal Science and Veterinary Medicine, Sher-e-Bangla Agricultural University, Dhaka, Bangladesh
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Md. Abdul Masum
Taro Horino
5Department of Endocrinology, Metabolism and Nephrology, Kochi Medical School, Kochi University, Nankoku, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yuki Otani
1Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Takashi Namba
1Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Takashi Namba
Teppei Nakamura
1Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan
6Department of Biological Safety Research, Food Research Laboratories, Chitose, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Teppei Nakamura
Elewa Yaser Hosny Ali
1Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan
7Department of Histology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yasuhiro Kon
1Laboratory of Anatomy, Department of Basic Veterinary Sciences, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Yasuhiro Kon
  • Article
  • Figures & Data Supps
  • Info & Metrics
  • View PDF
Loading

This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.

Visual Abstract

Figure
  • Download figure
  • Open in new tab
  • Download powerpoint

Significance Statement

Tertiary lymphoid structures (TLSs) form in organs exhibiting chronic inflammation. Immune responses to infections, autoimmune responses, or allergic responses may trigger TLS development. We observed urine–urothelium barrier alterations in the renal pelvis of a mouse model and in human subjects with chronic nephritis, with or without infection. Furthermore, urine leaked from the renal lumen into the parenchyma in nephritic mice. This stimulated the production of cytokines/chemokines in renal stromal cells, resulting in TLS development termed “urinary tract–associated lymphoid structures” (UTALSs). UTALS development correlated with chronic nephritis in humans and mice regardless of UTI, thus possibly revealing a novel pathologic mechanism. Elucidation is crucial for better understanding of noninfectious chronic nephritis.

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-γ 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-γ, TNF-α) 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-α/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.

  • chemokine
  • immunology and pathology
  • kidney anatomy
  • chronic inflammation
  • fibroblast
  • histopathology
  • nephritis
  • pathology
  • pathophysiology of renal disease and progression
  • pyelonephritis
  • Copyright © 2022 by the American Society of Nephrology
View Full Text

If you are:

  • an ASN member, select the "ASN Member" login button. 
  • an individual subscriber, login with you User Name and Password.
  • an Institutional user, select the Institution option where you will be presented with a list of Shibboleth federations. If you do not see your federation, contact publications@asn-online.org. 

ASN MEMBER LOGIN

ASN MEMBER LOGIN

Log in using your username and password

Forgot your user name or password?

Log in through your institution

You may be able to gain access using your login credentials for your institution. Contact your library if you do not have a username and password.

Purchase access

Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$34.00

In order to get access to the article, you must have an account.  If you have an account, enter your user name and password into the boxes above. If you do not have an account, follow the instructions below to create one.  Once you have purchased the article, you will have access to it for 24 hours.  

Steps for Creating an Account:

Click the "Purchase Access" button.  The page will redisplay with the following message at the top of the screen. In the message, click to create an account. 

When you create the account, you will be asked to register a user name, email address and you will need to create a password that is at least eight characters in length.  You do not need an ASN Member number to complete the form. As you move through the registration page, you will have to verify you are a person by completing a Captcha request.   Lastly, your first and last name will be required. 

Once your information is successfully saved, the system will redisplay the home page of the journal.  From there, navigate back to the article to purchase.  Select the article and at the bottom of the page, use the credentials you just created to login. The article will be added to your shopping cart.  You can continue to navigate across JASN and CJASN adding to your cart from both journals. When you are ready to complete your purchse, select the Shopping Cart from the upper right hand corner of the page and follow the onscreen instructions. 

PreviousNext
Back to top

In this issue

Journal of the American Society of Nephrology: 33 (1)
Journal of the American Society of Nephrology
Vol. 33, Issue 1
January 2022
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
View Selected Citations (0)
Print
Download PDF
Sign up for Alerts
Email Article
Thank you for your help in sharing the high-quality science in JASN.
Enter multiple addresses on separate lines or separate them with commas.
Close Association between Altered Urine–Urothelium Barrier and Tertiary Lymphoid Structure Formation in the Renal Pelvis during Nephritis
(Your Name) has sent you a message from American Society of Nephrology
(Your Name) thought you would like to see the American Society of Nephrology web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Close Association between Altered Urine–Urothelium Barrier and Tertiary Lymphoid Structure Formation in the Renal Pelvis during Nephritis
Osamu Ichii, Marina Hosotani, Md. Abdul Masum, Taro Horino, Yuki Otani, Takashi Namba, Teppei Nakamura, Elewa Yaser Hosny Ali, Yasuhiro Kon
JASN Jan 2022, 33 (1) 88-107; DOI: 10.1681/ASN.2021040575

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Request Permissions
Share
Close Association between Altered Urine–Urothelium Barrier and Tertiary Lymphoid Structure Formation in the Renal Pelvis during Nephritis
Osamu Ichii, Marina Hosotani, Md. Abdul Masum, Taro Horino, Yuki Otani, Takashi Namba, Teppei Nakamura, Elewa Yaser Hosny Ali, Yasuhiro Kon
JASN Jan 2022, 33 (1) 88-107; DOI: 10.1681/ASN.2021040575
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like

Jump to section

  • Article
    • Visual Abstract
    • Abstract
    • Methods
    • Results
    • Discussion
    • Disclosures
    • Funding
    • Acknowledgments
    • Data Sharing Statement
    • Supplemental Material
    • Footnotes
    • References
  • Figures & Data Supps
  • Info & Metrics
  • View PDF

More in this TOC Section

  • Impaired Mineral Ion Metabolism in a Mouse Model of Targeted Calcium-Sensing Receptor (CaSR) Deletion from Vascular Smooth Muscle Cells
  • Factor H–Related Protein 1 Drives Disease Susceptibility and Prognosis in C3 Glomerulopathy
  • Tumor Lysis Syndrome and AKI: Beyond Crystal Mechanisms
Show more Basic Research

Cited By...

  • No citing articles found.
  • Google Scholar

Similar Articles

Related Articles

  • This Month's Highlights
  • A Novel Pathological Mechanism of Tertiary Lymphoid Structure Formation in the Renal Pelvis
  • PubMed
  • Google Scholar

Keywords

  • chemokine
  • immunology and pathology
  • kidney anatomy
  • chronic inflammation
  • fibroblast
  • histopathology
  • nephritis
  • pathology
  • pathophysiology of renal disease and progression
  • pyelonephritis

Articles

  • Current Issue
  • Early Access
  • Subject Collections
  • Article Archive
  • ASN Annual Meeting Abstracts

Information for Authors

  • Submit a Manuscript
  • Author Resources
  • Editorial Fellowship Program
  • ASN Journal Policies
  • Reuse/Reprint Policy

About

  • JASN
  • ASN
  • ASN Journals
  • ASN Kidney News

Journal Information

  • About JASN
  • JASN Email Alerts
  • JASN Key Impact Information
  • JASN Podcasts
  • JASN RSS Feeds
  • Editorial Board

More Information

  • Advertise
  • ASN Podcasts
  • ASN Publications
  • Become an ASN Member
  • Feedback
  • Follow on Twitter
  • Password/Email Address Changes
  • Subscribe to ASN Journals

© 2022 American Society of Nephrology

Print ISSN - 1046-6673 Online ISSN - 1533-3450

Powered by HighWire