Interferon-γ production by tubulointerstitial human CD56bright natural killer cells contributes to renal fibrosis and chronic kidney disease progression

• DOI: 10.1016/j.kint.2017.02.006
• Publication Date: 2017-04-08T07:32:08Z
• Authors: Becker M.P. Law; Ray Wilkinson; Xiangju Wang; Katrina Kildey; Mae Lindner; Melissa J. Rist; Kenneth Beagley; Helen Healy; Andrew J. Kassianos
• Keywords: Innate lymphoid cell

Natural killer (NK) cells are a population of lymphoid that play significant role in mediating innate immune responses. Studies mice suggest pathological for NK models kidney disease. In this study, we characterized the cell subsets present native kidneys patients with tubulointerstitial fibrosis, hallmark chronic Significantly higher numbers total (CD3-CD56+) were detected renal biopsies fibrosis compared diseased without and healthy tissue using multi-color flow cytometry. At subset level, both CD56dim particularly CD56bright elevated fibrotic tissue. However, only significantly correlated loss function. Expression tissue-retention -activation molecule CD69 on was increased biopsy specimens non-fibrotic tissue, indicative pathogenic phenotype. Further cytometric phenotyping revealed selective co-expression activating receptor CD335 (NKp46) differentiation marker CD117 (c-kit) cells. Multi-color immunofluorescent staining localized accumulation within tubulointerstitium, (NKp46+ CD117+) identified as source pro-inflammatory cytokine interferon-γ compartment. Thus, activated interferon-γ–producing positioned to key process progression