A pilot study to assess peripheral blood TCR β-chain CDR3 repertoire in occupational medicamentosa-like dermatitis due to trichloroethylene using high-throughput sequencing

Lin, Dafeng; Wang, Dianpeng; Li, Peimao; Yang, Yanhua; Liu, Wei; Zhang, Liuzhuo; Zhang, Zhimin; Zhang, Yanfang; Huang, Xianqing

doi:10.1016/j.etap.2019.103211

Cited by 3 publications

(14 citation statements)

References 18 publications

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“…Dynamic analysis of OMDT TCR repertoires started with the repertoire diversity. As reported previously in the pilot cross-sectional study 8 , we found no significant difference in CDR3 repertoire diversity measured by 6 indices between the cases and the controls, although decreased diversity has been observed in similar diseases 10 – 12 . Remarkably, the 6 indices all showed an increasing trend with the decreasing severity from acute to recovery stage in the cases, however, the differences between the stages were not statistically significant.…”

Section: Discussionsupporting

confidence: 85%

“…We next examined TRBV/TRBD/TRBJ usage and combination, and found that only TRBV6-4 and TRBV7-9 usage were significantly associated with OMDT, and 5 of their combinations with TRBJ were further identified to be OMDT severity-related. In the previous cross-sectional study 8 , we also identified that TRBV6-4 frequencies of the cases were significantly lower than the controls ( P < 0.05), and TRBV7-9 frequencies were higher in the cases, but the difference with the controls was not statistically significant. It seems that the time point of repertoire detection is quite critical, because we found in this longitudinal study that only the cases in acute stage showed significantly higher TRBV7-9 frequencies than the controls, suggesting the importance of dynamic analysis in studies of TCR repertoire.…”

Section: Discussionmentioning

confidence: 55%

“…TCR is the key to initiate T cell reactions, therefore, studying TCR is of great significance for the treatment and prevention of OMDT. Previously, we had explored cross-sectionally the characteristics of TCR repertoires from OMDT patients 8 ; the dynamic features of OMDT TCR repertoires were further analyzed in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…Previously, we conducted a case–control study to explore the characteristics of TCR repertoires in OMDT by the high-throughput sequencing (HTS) of the TCR β-chain CDR3 8 . In the previous, cross-sectional study, we found 5 TCR β-chain V gene (TRBV) and 1 TCR β-chain J gene (TRBJ) usage, and 48 TRBV-TRBJ combinations that might be related to OMDT.…”

Section: Introductionmentioning

confidence: 99%

“…In the previous, cross-sectional study, we found 5 TCR β-chain V gene (TRBV) and 1 TCR β-chain J gene (TRBJ) usage, and 48 TRBV-TRBJ combinations that might be related to OMDT. We also identified 17 CDR3 nucleotide (nt) sequences and 16 CDR3 amino acid (aa) sequences of which the corresponding T cell clones might be specific to OMDT and participate in OMDT development 8 . However, the human TCR repertoire is quite sophisticated, and it actually dynamically shifts with the disease status.…”

Section: Introductionmentioning

confidence: 99%

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Dynamic analysis of peripheral blood TCR β-chain CDR3 repertoire in occupational medicamentosa-like dermatitis due to trichloroethylene

Lin

Wang

et al. 2021

Sci Rep

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Previously, we had cross-sectionally explored the characteristics of T cell receptor (TCR) repertoires from occupational medicamentosa-like dermatitis due to trichloroethylene (OMDT) patients, now we further analyzed the dynamic features of OMDT TCR repertoires. Peripheral blood TCR β-chain complementarity-determining region 3 (CDR3) genes were detected with the high throughput sequencing in 24 OMDT cases in their acute, chronic and recovery stages, respectively, and in 24 trichloroethylene-exposed healthy controls. The TCR repertoire diversity, TRBV/TRBD/TRBJ gene usage and combination, frequencies of CDR3 nucleotide (nt) and amino acid (aa) sequences in the cases in different stages and in the controls were analyzed. TRBV6-4 and TRBV7-9 frequencies significantly differed between the cases and controls (both P < 6.1 × 10–4). TRBV6-4 combination with TRBJ2-1, TRBJ2-2, TRBJ2-3, and TRBJ2-6, and TRBV7-9 combination with TRBJ2-1 were associated with the stage by OMDT severity (all P < 0.001). Ten CDR3-nt and 7 CDR3-aa sequences in TRBV7-9-TRBJ2-1 combination and 1 CDR3-nt and 1 CDR3-aa sequences in TRBV6-4-TRBJ2-1 combination were identified as associated with the severity of OMDT (all P < 0.001). We revealed further how TCR repertoires vary with the severity in the development of OMDT, and severity-related TCRs may provide important therapeutic targets for OMDT in clinical practice.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Dynamic analysis of peripheral blood TCR β-chain CDR3 repertoire in occupational medicamentosa-like dermatitis due to trichloroethylene

Lin

Wang

et al. 2021

Sci Rep

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C5b-9 mediates ferroptosis of tubular epithelial cells in trichloroethylene-sensitization mice

Liu

Zuo

et al. 2022

Ecotoxicology and Environmental Safety

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Glomerular Damage in Trichloroethylene-Sensitized Mice: Targeting Cathepsin L-Induced Hyperactive mTOR Signaling

et al. 2021

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Trichloroethylene (TCE) is a serious health hazard for workers with daily exposure, causing occupational medicamentosa-like dermatitis due to TCE (OMDT) and glomerular damage. Recent studies suggest that mTORC1 signaling is activated in various glomerular disorders; however, the role of mTORC1 signaling in TCE-induced glomerular damage remains to be explored. In the present study, 6 OMDT patients were enrolled and a TCE-sensitized mouse model was established to investigate molecular mechanisms underlying the glomerular damage associated with OMDT. Glomerular damage was assessed by levels of urine nephrin, H&E staining, and renal function test. Ultrastructural change of podocyte was investigated by transmission electron microscopy. The podocyte-related molecules including nephrin, α-actinin-4, and integrin β1 were visualized by immunofluorescence. The activation of mTORC1 signaling was confirmed by Western blot. Glomerular apoptosis was examined by the TUNEL test and Western blotting. Expression and location of cathepsin L (CTSL) were assessed by RT-PCR and immunofluorescence. Our results showed that TCE sensitization caused damage to glomerular structural integrity and also increased the activation of mTORC1 signaling, which was accompanied by podocyte loss, hypertrophy, and glomerular apoptosis. Importantly, we also found that over-expressed CTSL was mainly located in podocyte and CTSL inhibition could partially block the activation of mTORC1 signaling. Thus, our findings suggested a novel mechanism whereby hyperactive mTOR signaling contributes to TCE sensitization–induced and immune-mediated glomerular damage via CTSL activation.

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A pilot study to assess peripheral blood TCR β-chain CDR3 repertoire in occupational medicamentosa-like dermatitis due to trichloroethylene using high-throughput sequencing

Cited by 3 publications

References 18 publications

Dynamic analysis of peripheral blood TCR β-chain CDR3 repertoire in occupational medicamentosa-like dermatitis due to trichloroethylene

Dynamic analysis of peripheral blood TCR β-chain CDR3 repertoire in occupational medicamentosa-like dermatitis due to trichloroethylene

C5b-9 mediates ferroptosis of tubular epithelial cells in trichloroethylene-sensitization mice

Glomerular Damage in Trichloroethylene-Sensitized Mice: Targeting Cathepsin L-Induced Hyperactive mTOR Signaling

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