Kidney injury in response to crystallization of calcium oxalate leads to rearrangement of the intrarenal T cell receptor delta immune repertoire

Abstract

Background: Calcium oxalate (CaOx), the major constituent of most kidney stones, induces inflammatory infiltration and injures renal tubular cells. However, the role of γδT cells in CaOx-mediated kidney injury remains unclear. Therefore, this study investigated the distribution of intrarenal γδT cells and T cell receptor δ(TCRδ) immune repertoires in response to interactions with CaOx crystals. Methods: CaOx crystal mouse model was established by glyoxylate injection. Flow cytometer was used to analyze the expression of CD69 and IL-17 from intrarenal γδT cells. Furthermore, TCR immune repertoire sequencing (IR-Seq) was used to monitor the profile of the TCRδimmune repertoire. Results: Our results indicated that CaOx crystals lead to obvious increases in the expression and activation of intrarenal γδT cells. In TCRδimmune repertoire, the majority of V/J gene and V-J/V-D-J combination segments, barring individual exceptions, were similar between kidneys with CaOx formation and control kidneys. Impressively, high complementarity determining region 3 (CDR3) diversity was observed in response to CaOx crystal formation along with distinct CDR3 distribution and abundance. Conclusion: Our work suggests the presence of aberrant γδT cell activation and reconstitution of the TCRδimmune repertoire in response to CaOx crystal deposition.