DRESS 中调节性 T 细胞的失调与自身免疫后遗症:流式细胞仪和 NanoString 分析的启示

IF 3.5 3区 医学 Q1 DERMATOLOGY
Suparada Khanaruksombat, Supranee Buranapraditkul, Pattarawat Thantiworasit, Nithikan Suthumchai, Pawinee Rerknimitr, Rangsima Reantragoon, Jettanong Klaewsongkram
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引用次数: 0

摘要

伴有嗜酸性粒细胞增多和全身症状的药物反应(DRESS)和史蒂文斯-约翰逊综合征/毒性表皮坏死(SJS/TEN)是严重的皮肤超敏反应,具有不同的临床表现。调节性 T(Treg)细胞在这些综合征中的表现可能不同,从而导致了它们不同的临床特征和结果。本研究比较了 DRESS 和 SJS/TEN 患者在急性期和恢复期的 Treg 动态。流式细胞术定量分析并定义了 DRESS 和 SJS/TEN 患者血液中 CD4+CD25+CD127-FoxP3+ Tregs 的免疫表型,结果显示,与 DRESS 患者恢复期和 SJS/TEN 患者急性期相比,DRESS 患者急性期的 Treg 百分比最低。在急性期,伴有和不伴有自身免疫后遗症的DRESS患者Tregs中的CTLA-4表达均显著增加,而与健康对照组相比,只有不伴有自身免疫后遗症的DRESS患者的OX40表达升高。在SJS/TEN患者的急性期,还观察到Tregs中IL-10的高表达。与SJS/TEN相比,DRESS患者Tregs的抑制功能较低,这是通过自体Treg和效应T细胞共培养的抑制试验确定的。此外,NanoString 技术还检测了 Tregs 的 mRNA 图谱。研究发现,与JAK/STAT通路相关的基因在DRESS患者的急性期被下调,这些患者后来出现了自身免疫后遗症。我们的研究结果表明,与SJS/TEN相比,DRESS患者的Treg功能受损。JAK/STAT通路的早期紊乱可作为DRESS患者自身免疫发展的预后标志。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Dysregulation of Regulatory T Cells and Autoimmune Sequelae in DRESS: Insights From Flow Cytometry and NanoString Analysis

Drug reactions with eosinophilia and systemic symptoms (DRESS) and Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) are severe cutaneous adverse hypersensitivity reactions with distinct clinical manifestations. Regulatory T (Treg) cells may behave differently in these syndromes, contributing to their diverse clinical features and outcomes. This study compared Treg dynamics between DRESS and SJS/TEN patients during the acute and recovery phases. Flow cytometry quantitatively analysed and defined the immunophenotype of CD4+CD25+CD127FoxP3+ Tregs in blood from DRESS and SJS/TEN patients indicated that Treg percentages were lowest in DRESS patients during the acute phase compared to those in the recovery phase in DRESS patients and the acute phase in SJS/TEN patients. During the acute phase, CTLA-4 expression in Tregs in both DRESS patients with and without autoimmune sequelae was significantly increased, while only DRESS patients without autoimmune sequelae had elevated OX40 expression compared to the healthy controls. High IL-10 expression in Tregs during the acute phase in SJS/TEN patients was also observed. The suppressive function of Tregs was lower in DRESS compared to SJS/TEN, which was determined using a suppression assay by co-culturing autologous Treg and effector T cells. Furthermore, NanoString technology explored mRNA profiles in Tregs. Genes associated with the JAK/STAT pathway were found to be downregulated during the acute phase in DRESS patients who later developed autoimmune sequelae. Our findings evidenced impaired Treg function in DRESS compared to SJS/TEN. The early disturbance of the JAK/STAT pathway may serve as a prognostic marker for autoimmune development in DRESS patients.

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来源期刊
Experimental Dermatology
Experimental Dermatology 医学-皮肤病学
CiteScore
6.70
自引率
5.60%
发文量
201
审稿时长
2 months
期刊介绍: Experimental Dermatology provides a vehicle for the rapid publication of innovative and definitive reports, letters to the editor and review articles covering all aspects of experimental dermatology. Preference is given to papers of immediate importance to other investigators, either by virtue of their new methodology, experimental data or new ideas. The essential criteria for publication are clarity, experimental soundness and novelty. Letters to the editor related to published reports may also be accepted, provided that they are short and scientifically relevant to the reports mentioned, in order to provide a continuing forum for discussion. Review articles represent a state-of-the-art overview and are invited by the editors.
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