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寻常型天疱疮中产生增强干扰素γ的1型固有淋巴细胞和产生白细胞介素17的3型固有淋巴细胞:可能的治疗靶点。

Augmented IFNγ producing ILC1 and IL 17 producing ILC3 in pemphigus vulgaris: Plausible therapeutic target.

作者信息

Hooda Vishakha, Khandpur Sujay, Sharma Alpana

机构信息

Department of Biochemistry, AIIMS, New Delhi, India.

Department of Dermatology and Venereology, AIIMS, New Delhi, India.

出版信息

Cell Immunol. 2025 Feb;408:104910. doi: 10.1016/j.cellimm.2024.104910. Epub 2024 Dec 18.

Abstract

Innate Lymphoid cells (ILCs) are innate counterparts of helper T cells. Although low in number, they have proven to play major roles in many autoimmune diseases. In Pemphigus Vulgaris (PV), the gaps in the knowledge of functional role of ILCs remain. To bridge the gap, our study investigated the phenotype along with the functional determinants of ILCs involved in PV immunopathogenesis. Our data suggested augmentation in overall ILC population in circulation of PV patients. Specifically, ILC1 and ILC3 subtypes were significantly increased in peripheral circulation of PV patients compared to healthy controls. We observed no changes in ILC2 population. mRNAs from ILC enriched population showed significant upregulation in transcription factors- ID2, T bet and RORγt and a downregulation in GATA3 and RORα. The mRNA levels of ILC related cytokines- IFNγ and IL17 were significantly upregulated while no change was observed in the levels of IL13, IL 22, AHR. The levels of autoantibodies against desmoglein (Dsg) 3 which is the characteristic of PV pathogenesis were also checked in the serum which confirmed significant upregulation in PV patients. The levels of proinflammatory- IFNγ, IL 17 and IL 15 were elevated and anti-inflammatory cytokines- IL10 was downregulated in the serum of PV patients. The results of this study offer insights into the functional attributes of ILCs and related cytokines, potentially contributing to the development of future therapeutic interventions.

摘要

固有淋巴细胞(ILCs)是辅助性T细胞的固有对应物。尽管数量较少,但它们已被证明在许多自身免疫性疾病中起主要作用。在寻常型天疱疮(PV)中,关于ILCs功能作用的认识仍存在空白。为了填补这一空白,我们的研究调查了参与PV免疫发病机制的ILCs的表型及其功能决定因素。我们的数据表明PV患者循环中ILCs的总体数量增加。具体而言,与健康对照相比,PV患者外周循环中的ILC1和ILC3亚型显著增加。我们观察到ILC2数量没有变化。来自富含ILC的群体的mRNA显示转录因子ID2、T-bet和RORγt显著上调,而GATA3和RORα下调。ILC相关细胞因子IFNγ和IL-17的mRNA水平显著上调,而IL-13、IL-22、AHR的水平没有变化。血清中还检测了针对桥粒芯糖蛋白(Dsg)3的自身抗体水平,这是PV发病机制的特征,结果证实PV患者血清中该抗体水平显著上调。PV患者血清中促炎细胞因子IFNγ、IL-17和IL-15水平升高,抗炎细胞因子IL-10水平下调。本研究结果为ILCs和相关细胞因子的功能特性提供了见解,可能有助于未来治疗干预措施的开发。

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