Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Pancreatic Cancer (Jul 2025)
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
CD153/CD30 signaling promotes age-dependent tertiary lymphoid tissue expansion and kidney injury
Yuki Sato, … , Nagahiro Minato, Motoko Yanagita
Yuki Sato, … , Nagahiro Minato, Motoko Yanagita
Published November 23, 2021
Citation Information: J Clin Invest. 2022;132(2):e146071. https://doi.org/10.1172/JCI146071.
View: Text | PDF
Research Article Inflammation Nephrology Article has an altmetric score of 43

CD153/CD30 signaling promotes age-dependent tertiary lymphoid tissue expansion and kidney injury

  • Text
  • PDF
Abstract

Tertiary lymphoid tissues (TLTs) facilitate local T and B cell interactions in chronically inflamed organs. However, the cells and molecular pathways that govern TLT formation are poorly defined. Here, we identified TNF superfamily CD153/CD30 signaling between 2 unique age-dependent lymphocyte subpopulations, CD153+PD-1+CD4+ senescence-associated T (SAT) cells and CD30+T-bet+ age-associated B cells (ABCs), as a driver for TLT expansion. SAT cells, which produced ABC-inducing factors IL-21 and IFN-γ, and ABCs progressively accumulated within TLTs in aged kidneys after injury. Notably, in kidney injury models, CD153 or CD30 deficiency impaired functional SAT cell induction, which resulted in reduced ABC numbers and attenuated TLT formation with improved inflammation, fibrosis, and renal function. Attenuated TLT formation after transplantation of CD153-deficient bone marrow further supported the importance of CD153 in immune cells. Clonal analysis revealed that SAT cells and ABCs in the kidneys arose from both local differentiation and recruitment from the spleen. In the synovium of aged rheumatoid arthritis patients, T peripheral helper/T follicular helper cells and ABCs also expressed CD153 and CD30, respectively. Together, our data reveal a previously unappreciated function of CD153/CD30 signaling in TLT formation and propose targeting the CD153/CD30 signaling pathway as a therapeutic target for slowing kidney disease progression.

Authors

Yuki Sato, Akiko Oguchi, Yuji Fukushima, Kyoko Masuda, Naoya Toriu, Keisuke Taniguchi, Takahisa Yoshikawa, Xiaotong Cui, Makiko Kondo, Takeshi Hosoi, Shota Komidori, Yoko Shimizu, Harumi Fujita, Li Jiang, Yingyi Kong, Takashi Yamanashi, Jun Seita, Takuya Yamamoto, Shinya Toyokuni, Yoko Hamazaki, Masakazu Hattori, Yasunobu Yoshikai, Peter Boor, Jürgen Floege, Hiroshi Kawamoto, Yasuhiro Murakawa, Nagahiro Minato, Motoko Yanagita

×

Figure 4

SAT cells and ABCs progressively and correlatively expand within TLTs following kidney injury.

Options: View larger image (or click on image) Download as PowerPoint
SAT cells and ABCs progressively and correlatively expand within TLTs fo...
(A and B) Representative FACS plots and quantification of the frequencies of (A) SAT cells and (B) ABCs and germinal center B cells (GCB cells) in aged kidneys at various time points following ischemic reperfusion injury (IRI). (C) The correlation between the frequencies of SAT cells and the sum of the frequencies of ABCs and GCB cells in A and B (n = 3/time point; day 0, 4, 24, 45, and 60). (D) Immunofluorescence (IF) of GFP and CD45, CD3ε, B220, CD11c, p75 neurotrophin receptor (p75NTR), CD21, Ki67, and p21 in the kidneys of aged Spp1-EGFP-KI mice subjected to IRI. The white arrows indicate the localization of TLTs. Magnified views of the outlined box are shown on the right. (E) IF of GFP and CD45; GFP, B220, and CD21; and quantification of the number of CD45+GFP+ cells and CD21– B cells within TLTs in the renal cortex in serial sections of aged Spp1-EGFP-KI mouse kidneys at various time points following IRI (n = 3/time point; day 0, 4, 24, and 60). (F) The correlation between the number of CD45+GFP+ cells and CD21– B cells in E. Scale bars: 50 μm (D and E). Data are presented as mean ± SD. Statistical significance was determined by trend test, and correlation was determined by Pearson’s correlation analysis. *P < 0.05; **P < 0.01.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts

Picked up by 5 news outlets
Posted by 13 X users
60 readers on Mendeley
See more details