Dataset Information

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 ??T cells in CaOx-mediated kidney injury remains unclear. Therefore, this study investigated the distribution of intrarenal ??T cells and T cell receptor ? (TCR?) 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 ??T cells. Furthermore, TCR immune repertoire sequencing (IR-Seq) was used to monitor the profile of the TCR? immune repertoire.

Results

Our results indicated that CaOx crystals lead to obvious increases in the expression and activation of intrarenal ??T cells. In TCR? 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.

Conclusion

Our work suggests the presence of aberrant ??T cell activation and reconstitution of the TCR? immune repertoire in response to CaOx crystal deposition.

SUBMITTER: Zhu C

PROVIDER: S-EPMC6704580 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Zhu Chao C Liang Qing Q Liu Yaqun Y Kong Deliang D Zhang Jie J Wang Hu H Wang Kejia K Guo Zhiyong Z

Journal of translational medicine 20190822 1

<h4>Background</h4>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.<h4>Methods</h4>CaOx crystal mouse model was established by glyoxylate injection. Flow cytomete ...[more]

PMID: 31438987

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Project description:An indole-reacted calcium oxalate crystallization index (iCOCI) test was developed to quantify the total competence of urine to precipitate calcium oxalate (CaOx) crystals. We conducted the prospective cohort study in accordance with the STARD guideline to evaluate the accuracy of urinary iCOCI test (index test) for diagnosing urolithiasis. A total of 281 participants were recruited for the study. Levels of urinary iCOCI were determined in the pre-diagnostic 24-h urine samples. Positive urinary iCOCI (? 0.6 COM eqv., g/L) was accounted for 51% (144/281), and the rest of 49% (137/281) were negative. Non-contrast CT imaging (reference standard) was subsequently performed for the definite diagnosis of urolithiasis to divide the participants into two groups, non-stone subjects (NSS, n?=?122) and stone-forming subjects (SFS, n?=?159). It should be noted that only subjects who currently had urinary stone at the time of study were classified as SFS. Urinary iCOCI levels in the SFS were significantly higher than the NSS. ROC analysis revealed an area under curve (AUC) of 0.893 (95% CI: 0.855-0.932) in separating NSS from all SFS. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, positive likelihood ratio (LH+) and negative likelihood ratio (LH-) of urinary iCOCI test for diagnosis of all urolithiasis were 87%, 80%, 84%, 84%, 83%, 4.44 and 0.16, respectively. Of 159 SFS, 38 were confirmed to have CaOx stones. Among these 38 CaOx SFS, only 2 had negative urinary iCOCI test. The AUC of urinary iCOCI test for separating CaOx SFS from NSS was markedly high (0.946, 95% CI: 0.914-0.978). Sensitivity, specificity, PPV, NPV, accuracy, LH+ and LH- of urinary iCOCI test for diagnosing CaOx urolithiasis were 95%, 86%, 68%, 98%, 88%, 6.80 and 0.06, respectively. Conclusion, we clinically validated that an innovative non-invasive urinary iCOCI test was highly accurate to diagnose urolithiasis, especially CaOx stone. With its high sensitivity and NPV, urinary iCOCI test is clinically intended to use as a screening test for CaOx urolithiasis. LH- of 0.06 indicates that negative result of urinary iCOCI test is highly accurate to rule out the CaOx stone formation. It is noted that urinary iCOCI level is expressed as arbitrary unit, and it is not directly related to the actual physiological level of urinary oxalate.

Project description:Tribulus terrestris has significant antilithiatic efficacy established via both in vitro as well as in vivo studies and is used in numerous anti-urolithiatic herbal formulations viz. Cystone, Uriflow, Uritone and Neeri. However, to fully utilize its antilithiatic potential, the influence of different extraction parameters on antilithiatic ability of T. terrestris aqueous extract needs elucidation. Thus, the current study was undertaken using statistically optimized extraction conditions for aqueous extract preparation. Response surface methodology was employed to observe the influence of three variables i.e. temperature (°C), time (h) and solid: liquid ratio (S: L) on the extraction yield (%) and protein content (mg/g) of T. terrestris aqueous extract. RSM results revealed that the high S:L ratio, low temperature and reduced incubation time were optimal conditions for aqueous extraction. Under such extraction conditions the protein content reached the value of 26.6±1.22 mg/g and the obtained extraction yield was 27.32±1.62%. The assessment of antilithiatic activity of 4 selected extracts (AE1-4), revealed enhanced nucleation and aggregation inhibition of calcium oxalate crystals with AE1 and AE2, which in addition significantly altered the size and morphology of calcium oxalate monohydrate (COM) crystals compared to AE3 and AE4. In vitro cell culture based studies on renal epithelial cells (MDCK, NRK-52E and PK 15) proved that the AE1 showed higher cytoprotective potency by increasing cell viability as compared to the oxalate treated group. The free radical scavenging activity of aqueous extract lowered the reactive oxygen specie's induced damage and potentially reduced the signals of programmed cell death due to oxalate injury. In addition, modulation of the COM crystal morphology was enhanced by AE1 as compared to AE2. The FTIR and GC-MS analysis of AE1, showed the presence of biomolecules which could aid in the attenuation of lithiatic process. In the light of these results the utility of the RSM approach to fully optimize the antilithiatic potential of T. terrestris cannot be undermined.

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

Similar Datasets

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