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Isolation of Double Negative αβ T Cells from the Kidney
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C/EBPδ Mediates Immunity to Renal Autoinflammatory Disorders in a Stage-specific Manner
Ipsita Dey1, Yang Li1, Tiffany C Taylor1
1University of Pittsburgh, Division of Rheumatology and Clinical Immunology, Pittsburgh, PA.
Journal of Immunology (Baltimore, Md. : 1950)
|July 31, 2024
Summary
CCAAT/enhancer-binding protein (C/EBP) δ is elevated in kidney disease and essential for its progression. However, C/EBPδ and IL-17 signaling have divergent roles in kidney fibrosis, suggesting stage-specific functions in disease pathogenesis.
Area of Science:
- Immunology
- Nephrology
- Molecular Biology
Background:
- Kidney disease poses a significant health and economic burden, necessitating novel therapeutic strategies.
- Th17 cells and IL-17 signaling are implicated in autoantibody-induced glomerulonephritis (AGN) pathogenesis.
- Downstream IL-17 signaling pathways in autoimmunity remain incompletely understood.
Purpose of the Study:
- To investigate the role of CCAAT/enhancer-binding protein (C/EBP) δ in the pathogenesis of kidney disease.
- To elucidate the downstream signaling pathways of IL-17 in autoimmune kidney disease.
- To determine the specific contributions of C/EBPδ and IL-17 to renal fibrotic events.
Main Methods:
- Analysis of kidney biopsies from human AGN patients and a mouse model of anti-glomerular basement membrane disease.
- Utilizing Cebpd knockout mice to assess disease susceptibility and pathology.
- Employing a nephrotoxic injury model with aristolochic acid I to evaluate fibrotic responses.
Main Results:
- C/EBPδ was elevated in human AGN kidney biopsies and a mouse model, with Cebpd deficiency conferring complete protection.
- C/EBPδ was required in the radioresistant compartment for GN pathology and induced kidney injury markers like Il6 and Lcn2.
- Contrary to expectations, deficiency in C/EBPδ or IL-17 receptor enhanced kidney fibrosis in a separate injury model.
Conclusions:
- C/EBPδ is a critical mediator in the pathogenesis of autoimmune kidney disease.
- IL-17 and C/EBPδ exhibit divergent, stage-specific roles in kidney disease progression and fibrosis.
- These findings highlight a complex interplay between IL-17 signaling and C/EBPδ in renal pathology.
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