Human Tissue-Resident Mucosal-Associated Invariant T (MAIT) Cells in Renal Fibrosis and CKD

• DOI: 10.1681/asn.2018101064
• Publication Date: 2019-06-11T20:05:13Z
• Authors: Becker M. P. Law; Ray Wilkinson; Xiangju Wang; Katrina Kildey; Kurt Giuliani; Kenneth W. Beagley; Jacobus Ungerer; Helen Healy; Andrew J. Kassianos
• Keywords: Nephrology

Mucosal-associated invariant T (MAIT) cells represent a specialized lymphocyte population associated with chronic inflammatory disorders. Little is known, however, about MAIT in diseases of the kidney, including CKD.To evaluate human native kidneys tubulointerstitial fibrosis, hallmark CKD, we used multicolor flow cytometry to identify, enumerate, and phenotype such from kidney tissue biopsy samples, immunofluorescence microscopy localize these cells. We cocultured primary proximal tubular epithelial (PTECs) under hypoxic (1% oxygen) conditions enable examination mechanistic interactions.We identified (CD3+ TCR Vα7.2+ CD161hi) healthy diseased tissues, detecting expression tissue-resident markers (CD103/CD69) on both states. Tissue samples fibrosis had significantly elevated numbers compared either nonfibrotic or kidneys. Furthermore, CD69 levels, also an established marker activation, were increased fibrotic samples. Immunofluorescent analyses accumulating adjacent PTECs. Notably, activated presence PTECs (modeling microenvironment) displayed upregulated cytotoxic molecules perforin granzyme B; observed corresponding significant increase PTEC necrosis cocultures.Our findings indicate that may contribute process CKD via complex interactions