HG HEALY1,2,3, B LAW1,2,4, X WANG1,2, K KILDEY1,2, K GIULIANI1,2, K BEAGLEY4, R WILKINSON1,2,3,4, A KASSIANOS1,2,3,4
1Pathology Queensland, Brisbane, Australia, 2Royal Brisbane and Women’s Hospital, Brisbane, Australia, 3University of Queensland, Brisbane, Australia, 4Queensland University of Technology, Brisbane, Australia
Aim: To functionally characterise mucosal-associated invariant T (MAIT) cells present in human chronic kidney disease (CKD).
Background: MAIT cells are a specialised lymphocyte population associated with chronic inflammatory disorders in peripheral tissues. To date, MAIT cell research has focused primarily on mucosal tissue, with limited studies on non-mucosal organs such as kidneys. In this study, we evaluated MAIT cells in human native kidneys with tubulointerstitial fibrosis, the pathological hallmark of CKD.
Methods: MAIT cells were identified, enumerated and phenotyped from human kidney tissue by multi-colour flow cytometry. Localisation of MAIT cells was performed by immunofluorescence microscopy. MAIT cells and human primary proximal tubular epithelial cells (PTEC) were co-cultured under hypoxic (1% O₂) conditions to examine mechanistic tubulointerstitial interactions.
Results: We detected significantly elevated numbers of MAIT cells (TCR-Vα7.2+ CD161++) in diseased biopsies with interstitial fibrosis compared with diseased biopsies without fibrosis and healthy kidney tissue. The increased numbers of MAIT cells also correlated significantly with loss of kidney function (eGFR). MAIT cells in fibrotic biopsies expressed cytokine receptors (IL-7Rα, IL-18Rα), activation receptor (NKG2D), extravasation marker (CD44) and tissue-resident markers (CD69, CD103 and CD49a). Immunofluorescent staining of fibrotic kidney tissue localised the accumulation of MAIT cells within the tubulointerstitial compartment, adjacent to PTEC. Notably, under in vitro pro-fibrotic/hypoxic conditions, PTEC induced the up-regulated expression of tissue-resident markers on MAIT cells.
Conclusion: We provide the first characterisation of MAIT cells in human kidney tissue. Collectively, our data suggest that human MAIT cells are retained as tissue-resident lymphocytes and are positioned to contribute to the fibrotic process via complex interactions with PTEC. Further dissection of kidney MAIT cells is now required for the development of novel CKD therapeutics.
A/Prof Helen Healy is the Head of the Conjoint Kidney Research Laboratory and Director of Kidney Health Service, RBWH. A/Prof Healy has pioneered research into PTEC-immune cell interactions in the human system. She has a particular research focus on using our understanding of the mechanisms of CKD to develop effective treatments for this common chronic disease.