IL-17 mediates neutrophil infiltration and renal fibrosis following recovery from ischemia reperfusion: compensatory role of natural killer cells in athymic rats.

Abstract

T cells have been implicated in the pathogenesis of acute kidney injury (AKI) and its progression to chronic kidney disease (CKD). Previous studies suggest that Th17 cells participate during the AKI-to-CKD transition, and inhibition of T cell activity by mycophenolate mofetil (MMF) or losartan attenuates the development of fibrosis following AKI. We hypothesized that T cell-deficient rats may have reduced levels of IL-17 cytokine leading to decreased fibrosis following AKI. Renal ischemis-reperfusion (I/R) was performed on T cell-deficient athymic rats (Foxn1rnu-/rnu-) and control euthymic rats (Foxn1rnu-/+), and CKD progression was hastened by unilateral nephrectomy at day 33 and subsequent exposure to 4.0% sodium diet. Renal fibrosis developed in euthymic rats and was reduced by MMF treatment. Athymic rats exhibited a similar degree of fibrosis, but this was unaffected by MMF treatment. FACS analysis demonstrated that the number of IL-17+ cells was similar between postischemic athymic vs. euthymic rats. The source of IL-17 production in euthymic rats was predominately from conventional T cells (CD3+/CD161-). In the absence of conventional T cells in athymic rats, a compensatory pathway involving natural killer cells (CD3-/CD161+) was the primary source of IL-17. Blockade of IL-17 activity using IL-17Rc receptor significantly decreased fibrosis and neutrophil recruitment in both euthymic and athymic rats compared with vehicle-treated controls. Taken together, these data suggest that IL-17 secretion participates in the pathogenesis of AKI-induced fibrosis possibly via the recruitment of neutrophils and that the source of IL-17 may be from either conventional T cells or NK cells.

• Authors: Purvi Mehrotra, Jason A Collett, Seth D McKinney, Jackson Stevens, Carlie M Ivancic, David P Basile
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 312 Issue 3 Pg. F385-F397 (03 01 2017) ISSN: 1522-1466 [Electronic] United States
• PMID: 27852609 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 the American Physiological Society.

Chemical References

• Forkhead Transcription Factors
• Il17a protein, rat
• Interleukin-17
• Whn protein

Topics

• Acute Kidney Injury (genetics, immunology, metabolism, pathology)
• Animals
• Disease Models, Animal
• Disease Progression
• Fibrosis
• Forkhead Transcription Factors (genetics)
• Genotype
• Interleukin-17 (immunology, metabolism)
• Kidney (immunology, metabolism, pathology)
• Killer Cells, Natural (immunology, metabolism)
• Lymphocyte Activation
• Male
• Neutrophil Infiltration
• Neutrophils (immunology, metabolism)
• Phenotype
• Rats, Nude
• Rats, Transgenic
• Renal Insufficiency, Chronic (genetics, immunology, metabolism, pathology)
• Reperfusion Injury (genetics, immunology, metabolism, pathology)
• Signal Transduction
• Time Factors