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203,234 studies31 sourcesUpdated 51 min ago
Peer-reviewedCC BY 4.0JCI Insight

Time-restricted feeding reverses kidney fibrosis through reducing CD8+ T cell infiltration in obese mice

  • Claudia J. Edell1,2
  • John D. Erickson1,2
  • Xiaofen Liu1,2
  • Savannah C. Walker1,2
  • Jackson Colson1,2
  • Michael Heim1,2
  • Pranav Nagila1,2
  • Kyle H. Moore1,2
  • Keri M. Kemp1,2
  • Kelly Hyndman1,2
  • Selene Meza-Perez3
  • Troy D. Randall3
7 more authors
  • Annye P. Bennett4
  • Anna G. Sorace4
  • Yu-Hua Dean Fang4,5
  • David M. Pollock1,2
  • Carmen De Miguel1,2
  • Julienne L. Carstens6
  • Jennifer S. Pollock1,2
6 affiliations
  1. 1Cardio-Renal Physiology & Medicine
  2. 2Division of Nephrology, Department of Medicine
  3. 3Division of Clinical Immunology & Rheumatology, Department of Medicine
  4. 4Department of Radiology
  5. 5Department of Neurology, and
  6. 6Department of Hematology and Oncology, Heersink School of Medicine, University of Alabama at Birmingham (UAB), Birmingham, Alabama, USA.
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Abstract

Obesity is a major risk factor for chronic kidney disease. Time-restricted feeding (TRF) shows promise to reduce kidney inflammation in chronic kidney disease. We hypothesized that TRF blunts kidney fibrosis in obese mice by mitigating T cell inflammation. We used a diet-induced obese mouse model fed a high-fat diet (DIO; 45% fat) ad libitum for 18 weeks followed by 2 weeks of TRF or ad libitum high-fat feeding. We found that TRF reversed kidney fibrosis as well as reduced kidney CD8+ T cells in DIO mice. Our study also reveals that DIO mice had increased kidney CD8+ T cell infiltration from the small intestine that was blunted with TRF. Furthermore, anti-CD8 intervention in DIO showed reduced kidney fibrosis and damage compared with anti-IgG–treated DIO mice. Single-cell RNA-seq data reveal that DIO increased, while TRF reduced, the frequency of a specific cluster of CD8+ T cells that featured high expression of exhaustion/activation genes. Spatial analyses showed DIO mice had significant infiltration of PD-1+CD8+ T cells near CD31+ endothelial cells that was diminished by TRF. In conclusion, this study shows that TRF reversed kidney fibrosis through reducing CD8+ T cell infiltration in obese mice.

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Cite

BibTeXRIS
BibTeX
@article{edell2026timerestricted,
  title = {{Time-restricted feeding reverses kidney fibrosis through reducing CD8+ T cell infiltration in obese mice}},
  author = {Claudia J. Edell and John D. Erickson and Xiaofen Liu and Savannah C. Walker and Jackson Colson and Michael Heim and Pranav Nagila and Kyle H. Moore and Keri M. Kemp and Kelly Hyndman and Selene Meza-Perez and Troy D. Randall and Annye P. Bennett and Anna G. Sorace and Yu-Hua Dean Fang and David M. Pollock and Carmen De Miguel and Julienne L. Carstens and Jennifer S. Pollock},
  journal = {JCI Insight},
  year = {2026},
  month = aug,
  doi = {10.1172/jci.insight.195335},
  url = {https://doi.org/10.1172/jci.insight.195335},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Time-restricted feeding reverses kidney fibrosis through reducing CD8+ T cell infiltration in obese mice
AU  - Claudia J. Edell
AU  - John D. Erickson
AU  - Xiaofen Liu
AU  - Savannah C. Walker
AU  - Jackson Colson
AU  - Michael Heim
AU  - Pranav Nagila
AU  - Kyle H. Moore
AU  - Keri M. Kemp
AU  - Kelly Hyndman
AU  - Selene Meza-Perez
AU  - Troy D. Randall
AU  - Annye P. Bennett
AU  - Anna G. Sorace
AU  - Yu-Hua Dean Fang
AU  - David M. Pollock
AU  - Carmen De Miguel
AU  - Julienne L. Carstens
AU  - Jennifer S. Pollock
PY  - 2026
DA  - 2026/08/20
JO  - JCI Insight
DO  - 10.1172/jci.insight.195335
UR  - https://doi.org/10.1172/jci.insight.195335
AB  - Obesity is a major risk factor for chronic kidney disease. Time-restricted feeding (TRF) shows promise to reduce kidney inflammation in chronic kidney disease. We hypothesized that TRF blunts kidney fibrosis in obese mice by mitigating T cell inflammation. We used a diet-induced obese mouse model fed a high-fat diet (DIO; 45% fat) ad libitum for 18 weeks followed by 2 weeks of TRF or ad libitum high-fat feeding. We found that TRF reversed kidney fibrosis as well as reduced kidney CD8+ T cells in DIO mice. Our study also reveals that DIO mice had increased kidney CD8+ T cell infiltration from the small intestine that was blunted with TRF. Furthermore, anti-CD8 intervention in DIO showed reduced kidney fibrosis and damage compared with anti-IgG–treated DIO mice. Single-cell RNA-seq data reveal that DIO increased, while TRF reduced, the frequency of a specific cluster of CD8+ T cells that featured high expression of exhaustion/activation genes. Spatial analyses showed DIO mice had significant infiltration of PD-1+CD8+ T cells near CD31+ endothelial cells that was diminished by TRF. In conclusion, this study shows that TRF reversed kidney fibrosis through reducing CD8+ T cell infiltration in obese mice.
SN  - 2379-3708
ER  -