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Characterization of the TCRβ repertoire of peripheral MR1-restricted MAIT cells in psoriasis vulgaris patients
Scientific Reports ( IF 3.8 ) Pub Date : 2023-11-28 , DOI: 10.1038/s41598-023-48321-z
Maja Jirouš Drulak 1 , Zvonimir Grgić 2 , Vera Plužarić 2, 3 , Marija Šola 3 , Teuta Opačak-Bernardi 1 , Barbara Viljetić 1 , Kristina Glavaš 4 , Maja Tolušić-Levak 3, 5 , Vlatka Periša 6, 7 , Martina Mihalj 3, 8 , Mario Štefanić 9 , Stana Tokić 2
Affiliation  

Psoriasis vulgaris (PV) is an inflammatory skin disease largely driven by aberrant αβT cells. Mucosal-associated invariant T (MAIT) cells, which constitute the largest circulating innate-like αβT cell community in human adults, are characterized by a semi-invariant TCRVα7.2 receptor and MR1-restricted affinity toward microbial metabolites. Limited MAIT TCRα diversity is complemented by a more variable TCRβ repertoire, but its footprint in the MAIT repertoire of PV patients has never been tested. Here, we used bulk TCRSeq, MiXCR, VDJTools, and Immunarch pipelines to decipher and compare TCRβ clonotypes from flow-sorted, peripheral TCRVα7.2+MR1-5-OP-RU-tet+MAIT cells from 10 PV patients and 10 healthy, matched controls. The resulting TCRβ collections were highly private and individually unique, with small public clonotype content and high CDR3β amino acid length variability in both groups. The age-related increase in the ‘hyperexpanded’ clonotype compartment was observed in PV, but not in healthy MAIT repertoires. The TCRβ repertoires of PV patients were also marked by skewed TRBV/TRBJ pairing, and the emergence of PV-specific, public CDR3β peptide sequences closely matching the published CDR3β record from psoriatic skin. Overall, our study provides preliminary insight into the peripheral MAIT TCRβ repertoire in psoriasis and warrants further evaluation of its diagnostic and clinical significance.



中文翻译:


寻常型银屑病患者外周 MR1 限制性 MAIT 细胞 TCRβ 库的表征



寻常型银屑病 (PV) 是一种炎症性皮肤病,主要由异常的 αβT 细胞驱动。粘膜相关不变 T (MAIT) 细胞构成了成人中最大的循环先天性 αβT 细胞群落,其特征是半不变 TCRVα7.2 受体和对微生物代谢物的 MR1 限制的亲和力。有限的 MAIT TCRα 多样性由更多可变的 TCRβ 库进行补充,但其在真性红细胞增多症患者 MAIT 库中的足迹从未经过测试。在这里,我们使用批量 TCRSeq、MiXCR、VDJTools 和 Immunarch 管道来破译和比较来自 10 名 PV 患者和 10 名健康人的流式分选外周 TCRVα7.2 + MR1-5-OP-RU-tet + MAIT 细胞的 TCRβ 克隆型。匹配的控件。由此产生的 TCRβ 集合具有高度私密性和个体独特性,两组中公共克隆型含量较小且 CDR3β 氨基酸长度变异性较高。在 PV 中观察到“过度扩张”克隆型区室与年龄相关的增加,但在健康的 MAIT 库中却没有观察到。 PV 患者的 TCRβ 库也以倾斜的 TRBV/TRBJ 配对为标志,并且出现了与银屑病皮肤中已发表的 CDR3β 记录密切匹配的 PV 特异性公共 CDR3β 肽序列。总体而言,我们的研究提供了对银屑病外周 MAIT TCRβ 全部成分的初步了解,并值得进一步评估其诊断和临床意义。

更新日期:2023-11-29
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