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.
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DOI:
10.1038/s41598-021-89431-w
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发表时间:
2021-05-11
期刊:
影响因子:
4.6
通讯作者:
Huang X
Huang X
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Lin D;Wang D;Li P;Yang X;Liu W;Huang L;Zhang Z;Zhang Y;Zhang W;Zhang N;Zhang M;Huang X

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此前,我们横断面探讨了三氯乙烯职业性药物样皮炎(OMDT)患者T细胞受体(TCR)库的特征,现在我们进一步分析OMDT TCR库的动态特征。通过高通量测序分别检测了 24 例急性期、慢性期和恢复期 OMDT 病例以及 24 例三氯乙烯暴露健康对照者的外周血 TCR β 链互补决定区 3 (CDR3) 基因。分析不同阶段病例和对照的TCR库多样性、TRBV/TRBD/TRBJ基因使用和组合、CDR3核苷酸(nt)和氨基酸(aa)序列的频率。 TRBV6-4 和 TRBV7-9 频率在病例和对照之间存在显着差异(均为 P < 6.1 × 10–4)。 TRBV6-4 与 TRBJ2-1、TRBJ2-2、TRBJ2-3 和 TRBJ2-6 的组合,以及 TRBV7-9 与 TRBJ2-1 的组合与 OMDT 严重程度的分期相关(所有 P < 0.001)。 TRBV7-9-TRBJ2-1组合中的10个CDR3-nt和7个CDR3-aa序列以及TRBV6-4-TRBJ2-1组合中的1个CDR3-nt和1个CDR3-aa序列被确定与OMDT的严重程度相关(所有P<0.001)。我们进一步揭示了 TCR 库如何随着 OMDT 发展的严重程度而变化,并且与严重程度相关的 TCR 可能为临床实践中的 OMDT 提供重要的治疗靶点。
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.
影响因子: --
作者:
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