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.

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