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

Claudia J. Edell; John D. Erickson; Xiaofen Liu; Savannah C. Walker; Jackson Colson; Michael Heim; Pranav Nagila; Kyle H. Moore; Keri M. Kemp; Kelly Hyndman; Selene Meza-Perez; Troy D. Randall; Annye P. Bennett; Anna G. Sorace; Yu-Hua Dean Fang; David M. Pollock; Carmen De Miguel; Julienne L. Carstens; Jennifer S. Pollock

doi:10.1172/jci.insight.195335

¹CardioRenal Physiology & Medicine, University of Alabama at Birmingham, Birmingham, United States of America

²Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, United States of America

³Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America

⁴Department of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, United States of America

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¹CardioRenal Physiology & Medicine, University of Alabama at Birmingham, Birmingham, United States of America

²Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, United States of America

³Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America

⁴Department of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, United States of America

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¹CardioRenal Physiology & Medicine, University of Alabama at Birmingham, Birmingham, United States of America

²Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, United States of America

³Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America

⁴Department of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, United States of America

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¹CardioRenal Physiology & Medicine, University of Alabama at Birmingham, Birmingham, United States of America

²Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, United States of America

³Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America

⁴Department of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, United States of America

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¹CardioRenal Physiology & Medicine, University of Alabama at Birmingham, Birmingham, United States of America

²Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, United States of America

³Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America

⁴Department of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, United States of America

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¹CardioRenal Physiology & Medicine, University of Alabama at Birmingham, Birmingham, United States of America

²Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, United States of America

³Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America

⁴Department of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, United States of America

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¹CardioRenal Physiology & Medicine, University of Alabama at Birmingham, Birmingham, United States of America

²Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, United States of America

³Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America

⁴Department of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, United States of America

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¹CardioRenal Physiology & Medicine, University of Alabama at Birmingham, Birmingham, United States of America

²Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, United States of America

³Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America

⁴Department of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, United States of America

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¹CardioRenal Physiology & Medicine, University of Alabama at Birmingham, Birmingham, United States of America

²Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, United States of America

³Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America

⁴Department of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, United States of America

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¹CardioRenal Physiology & Medicine, University of Alabama at Birmingham, Birmingham, United States of America

²Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, United States of America

³Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America

⁴Department of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, United States of America

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¹CardioRenal Physiology & Medicine, University of Alabama at Birmingham, Birmingham, United States of America

²Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, United States of America

³Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America

⁴Department of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, United States of America

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¹CardioRenal Physiology & Medicine, University of Alabama at Birmingham, Birmingham, United States of America

²Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, United States of America

³Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America

⁴Department of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, United States of America

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¹CardioRenal Physiology & Medicine, University of Alabama at Birmingham, Birmingham, United States of America

²Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, United States of America

³Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America

⁴Department of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, United States of America

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¹CardioRenal Physiology & Medicine, University of Alabama at Birmingham, Birmingham, United States of America

²Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, United States of America

³Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America

⁴Department of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, United States of America

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¹CardioRenal Physiology & Medicine, University of Alabama at Birmingham, Birmingham, United States of America

²Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, United States of America

³Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America

⁴Department of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, United States of America

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¹CardioRenal Physiology & Medicine, University of Alabama at Birmingham, Birmingham, United States of America

²Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, United States of America

³Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America

⁴Department of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, United States of America

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¹CardioRenal Physiology & Medicine, University of Alabama at Birmingham, Birmingham, United States of America

²Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, United States of America

³Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America

⁴Department of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, United States of America

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¹CardioRenal Physiology & Medicine, University of Alabama at Birmingham, Birmingham, United States of America

²Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, United States of America

³Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America

⁴Department of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, United States of America

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¹CardioRenal Physiology & Medicine, University of Alabama at Birmingham, Birmingham, United States of America

²Division of Clinical Immunology & Rheumatology, University of Alabama at Birmingham, Birmingham, United States of America

³Department of Radiology, University of Alabama at Birmingham, Birmingham, United States of America

⁴Department of Hematology and Oncology, University of Alabama at Birmingham, Birmingham, United States of America

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JCI Insight. https://doi.org/10.1172/jci.insight.195335.
Copyright © 2026, Edell et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Published August 28, 2026 - Version history

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 revealed 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 to anti-IgG treated DIO mice. Single cell RNA sequencing data revealed 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 discovered that TRF reverses kidney fibrosis through reducing CD8⁺ T cell infiltration in obese mice.

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

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