| First Author | Coppock GM | Year | 2020 |
| Journal | J Immunol | Volume | 205 |
| Issue | 2 | Pages | 377-386 |
| PubMed ID | 32522836 | Mgi Jnum | J:309273 |
| Mgi Id | MGI:6705718 | Doi | 10.4049/jimmunol.1901463 |
| Citation | Coppock GM, et al. (2020) Loss of IL-27Ralpha Results in Enhanced Tubulointerstitial Fibrosis Associated with Elevated Th17 Responses. J Immunol 205(2):377-386 |
| abstractText | Clinical and experimental studies have established that immune cells such as alternatively activated (M2) macrophages and Th17 cells play a role in the progression of chronic kidney disease, but the endogenous pathways that limit these processes are not well understood. The cytokine IL-27 has been shown to limit immune-mediated pathology in other systems by effects on these cell types, but this has not been thoroughly investigated in the kidney. Unilateral ureteral obstruction was performed on wild-type and IL-27Ralpha(-/-) mice. After 2 wk, kidneys were extracted, and the degree of injury was measured by hydroxyproline assay and quantification of neutrophil gelatinase-associated lipocalin mRNA. Immune cell infiltrate was evaluated by immunohistochemistry and flow cytometry. An anti-IL-17A mAb was subsequently administered to IL-27Ralpha(-/-) mice every 2 d from day of surgery with evaluation as described after 2 wk. After unilateral ureteral obstruction, IL-27 deficiency resulted in increased tissue injury and collagen deposition associated with higher levels of chemokine mRNA and increased numbers of M2 macrophages. Loss of the IL-27Ralpha led to increased infiltration of activated CD4(+) T cells that coproduced IL-17A and TNF-alpha, and blockade of IL-17A partially ameliorated kidney injury. Patients with chronic kidney disease had elevated serum levels of IL-27 and IL-17A, whereas expression of transcripts for the IL-27RA and the IL-17RA in the tubular epithelial cells of patients with renal fibrosis correlated with disease severity. These data suggest that endogenous IL-27 acts at several points in the inflammatory cascade to limit the magnitude of immune-mediated damage to the kidney. |
