Abstract
BackgroundCalcium 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.MethodsCaOx 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 TCRδ immune repertoire.ResultsOur results indicated that CaOx crystals lead to obvious increases in the expression and activation of intrarenal γδT cells. In TCRδ immune 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.ConclusionOur work suggests the presence of aberrant γδT cell activation and reconstitution of the TCRδ immune repertoire in response to CaOx crystal deposition.
Highlights
Calcium oxalate (CaOx), the major constituent of most kidney stones, induces inflammatory infiltration and injures renal tubular cells
Kidney stones, which primarily settle in the kidneys, are the most common disorder of the urinary tract, and their worldwide prevalence has increased over the decades [1]
The results indicated higher levels of intrarenal γδT cells in CaOxmediated kidney injury compared to healthy kidneys (Fig. 1b)
Summary
Calcium oxalate (CaOx), the major constituent of most kidney stones, induces inflammatory infiltration and injures renal tubular cells. The role of γδT cells in CaOx-mediated kidney injury remains unclear. This study investigated the distribution of intrarenal γδT cells and T cell receptor δ (TCRδ) immune repertoires in response to interactions with CaOx crystals. Kidney stones, which primarily settle in the kidneys, are the most common disorder of the urinary tract, and their worldwide prevalence has increased over the decades [1]. The most common renal stone component is CaOx, accounting for 65.9% of all stones. ΓδT cells normally account for 1–10% of circulating T lymphocytes, they constitute the major subset of resident T cells in the mucosa and organs [8, 9].
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