INTERLEUKIN (IL)-17 PRODUCTION BY TUBULOINTERSTITIAL HUMAN GAMMA-DELTA T CELLS IN RENAL FIBROSIS AND CHRONIC KIDNEY DISEASE

AJ KASSIANOS1,2,3,4, B LAW1,2,3, X WANG1,2, K KILDEY1,2, M LINDNER1,2,4, MJ RIST1,2, K BEAGLEY3, R WILKINSON1,2,3,4, H HEALY1,2

1Conjoint Kidney Laboratory, Pathology Queensland, Brisbane, Queensland; 2Kidney Health Service, Royal Brisbane and Women’s Hospital, Brisbane, Queensland; 3Queensland University of Technology, Brisbane, Queensland; 4Medical School, University of Queensland, Brisbane, Queensland

Aim: To characterise γ/δ T cells present in human fibrotic chronic kidney disease (CKD).

Background: γ/δ T cells are effector lymphocytes recognised as having important functional roles during chronic inflammatory processes. Mouse studies suggest a pathological role for γ/δ T cells in immune-mediated models of kidney disease. This study evaluates γ/δ T cells in human CKD.

Methods:  We extracted γ/δ T cells from healthy kidney tissue and diseased biopsies with and without fibrosis. γ/δ T cells were identified, enumerated and phenotyped by twelve-colour flow cytometry. Localisation of γ/δ T cells was examined by multi-colour immunofluorescent microscopy.

Results: We detected significantly elevated numbers of γ/δ T cells (CD45+CD3+γ/δ+) in diseased biopsies with interstitial fibrosis compared with diseased biopsies without fibrosis and healthy kidney tissue. The increased numbers of γ/δ T cells correlated significantly with loss of kidney function (eGFR). Immunofluorescent analysis of fibrotic kidney tissue localised the accumulation of γ/δ T cells within the tubulointerstitial compartment, adjacent to proximal tubular epithelial cells (PTEC), defined as tubular cells expressing aquaporin-1. Notably, we identified tubulointerstitial γ/δ T cells as a key source of pro-inflammatory cytokine IL-17.

Conclusion: The correlation of IL-17-producing γ/δ T cells with histologically and functionally more severe CKD suggests a pathological role. Further functional dissection of γ/δ T cells is now required for the development of therapeutics capable of blocking this previously untargeted immune cell population.

About ANZSN

The ASM is hosted by Australian and New Zealand Society of Nephrology.

The aims of the Society are to promote and support the study of the kidney and urinary tract in health and disease, and to ensure the highest professional standards for the practice of nephrology in Australia and New Zealand.

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