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Heterogeneous fibroblasts underlie age-dependent tertiary lymphoid tissues in the kidney
Open accessAbstract
Acute kidney injury (AKI) is a common clinical condition defined as a rapid decline in kidney function. AKI is a global health burden, estimated to cause 2 million deaths annually worldwide. Unlike AKI in the young, which is reversible, AKI in the elderly often leads to end-stage renal disease, and the mechanism that prevents kidney repair in the elderly is unclear. Here we demonstrate that aged but not young mice developed multiple tertiary lymphoid tissues (TLTs) in the kidney after AKI. TLT size was associated with impaired renal function and increased expression of proinflammatory cytokines and homeostatic chemokines, indicating a possible contribution of TLTs to sustained inflammation after injury. Notably, resident fibroblasts from a single lineage diversified into p75 neurotrophin receptor + (p75NTR + ) fibroblasts and homeostatic chemokine–producing fibroblasts inside TLTs, and retinoic acid–producing fibroblasts around TLTs. Deletion of CD4 + cells as well as late administration of dexamethasone abolished TLTs and improved renal outcomes. Importantly, aged but not young human kidneys also formed TLTs that had cellular and molecular components similar to those of mouse TLTs. Therefore, the inhibition of TLT formation may offer a novel therapeutic strategy for AKI in the elderly.
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“Moreover, older individuals become more susceptible to acute kidney injury (AKI) and chronic kidney disease (CKD).123,147”
From Inflammation and aging: signaling pathways and intervention therapies (2023) · cites this paper as [147]
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Metadata
- Authors
- Sato, Y., Mii, A., Hamazaki, Y., Fujita, H., Nakata, H., Masuda, K., Nishiyama, S., Shibuya, S., Haga, H., Ogawa, O., Shimizu, A., Narumiya, S., Kaisho, T., Arita, M., Yanagisawa, M., Miyasaka, M., Sharma, K., Minato, N., Kawamoto, H., & Yanagita, M.
- Affiliations
- Department of Nephrology,
- Department of Immunology and Cell Biology,
- Kyoto University (JP)
- Department of Diagnostic Pathology,
- Department of Urology,
- Kyoto University Hospital (JP)
- Medical Innovation Center, Graduate School of Medicine,
- Wakayama Medical University (JP)
- RIKEN Center for Integrative Medical Sciences (JP)
- Howard Hughes Medical Institute (US)
- University of Turku (FI)
- University of California San Diego (US)
- Corresponding author
- Yanagita, Motoko
- ORCID
- Venue
- JCI Insight
- Published
- 2016-07-21
- Volume
- 1
- Issue
- 11
- Pages
- e87680-e87680
- ISSN
- 2379-3708 (ISSN-L)
- PMC
- PMC5033938
- OpenAlex
- W2504280359
- Cited by
- 148
- References
- 53
- Citations by year
- 2026: 14 · 2025: 22 · 2024: 20 · 2023: 15 · 2022: 18 · 2021: 18 · 2020: 17 · 2019: 10 · 2018: 10 · 2017: 4
- FWCI
- 8.05
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- JCI Insight (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion, cc-by)
- UTUPub (University of Turku) (submittedVersion)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion, cc-by)
- Funders
- Boehringer Ingelheim Japan
- Kyowa Hakko Kirin
- Astellas Pharma
- Mitsubishi Tanabe Pharma Corporation
- Chugai Pharmaceutical
- Japan Society for the Promotion of Science (15H04743, 26293106, 24111008, 24111001, 15K15151, 16K09870, 15H01154, 26220207, 25293069)
- Daiichi Sankyo Europe
- Topics
- Health Sciences › Medicine › Nephrology › Acute Kidney Injury Research
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Keywords
- tertiary lymphoid tissue, acute kidney injury, aging, kidney fibroblasts, p75 neurotrophin receptor, retinoic acid, inflammatory cytokines, renal inflammation, CD4+ T cell depletion, dexamethasone, end-stage renal disease, kidney repair
- MeSH terms
- Adult, Age Factors, Aged, Animals, Fibroblasts, Humans, Kidney, Kidney Tubules, Lymphoid Tissue, Male, Mice, Inbred C57BL, Mice, Inbred ICR, Risk Factors, Receptors, Nerve Growth Factor, Chemokines, Mice, Acute Kidney Injury
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