Imai Yasutomo, Kusakabe Minori, Nagai Makoto, Yasuda Koubun, Yamanishi Kiyofumi
Department of Dermatology, Hyogo College of Medicine, Nishinomiya, Japan.
Department of Immunology, Hyogo College of Medicine, Nishinomiya, Japan.
JID Innov. 2021 Feb 20;1(1):100003. doi: 10.1016/j.xjidi.2021.100003. eCollection 2021 Mar.
Group 2 innate lymphoid cells (ILCs) are thought to contribute to the pathogenesis of atopic dermatitis (AD). IL-4 stimulates T helper type 2 (Th2) cells and ILC2s to proliferate and produce cytokines. Dupilumab, an antibody against the IL-4 receptor, is used in AD therapy. We speculated that its efficacy might involve blocking the activation of Th2 cells and ILC2s via IL-4. Here, we examined circulating Th2 cells and ILC2s in 27 Japanese patients with AD before and after the administration of dupilumab. Between 0 and 4 months after dupilumab administration, the percentages of Th2 cells and ILC2s were decreased. Notably, ILC2/3 ratio was decreased after dupilumab treatment. Interestingly, ILC2/3 ratio before dupilumab treatment were significantly higher in high responders than in low responders to dupilumab. To resolve the molecular signatures of the Th2 and ILC2s in AD, we sorted CD4 T cells and ILCs from peripheral blood and analyzed their transcriptomes using the BD Rhapsody Single-cell RNA sequencing system. Between 0 and 4 months after dupilumab administration, the Th2 and ILC2 cluster gene signatures were downregulated. Thus, dupilumab might improve dermatitis by suppressing the Th2 cell and ILC2 populations and altering the Th2 and ILC2 repertoire in patients with AD.
第2组固有淋巴细胞（ILC）被认为与特应性皮炎（AD）的发病机制有关。白细胞介素-4（IL-4）刺激2型辅助性T细胞（Th2）和ILC2增殖并产生细胞因子。度普利尤单抗是一种抗IL-4受体的抗体，用于AD治疗。我们推测其疗效可能涉及通过IL-4阻断Th2细胞和ILC2的激活。在此，我们检测了27例日本AD患者在使用度普利尤单抗前后循环中的Th2细胞和ILC2。在使用度普利尤单抗后的0至4个月内，Th2细胞和ILC2的百分比下降。值得注意的是，度普利尤单抗治疗后ILC2/3比值下降。有趣的是，在度普利尤单抗治疗前，高反应者的ILC2/3比值显著高于低反应者。为了解决AD中Th2和ILC2的分子特征，我们从外周血中分选了CD4 T细胞和ILC，并使用BD Rhapsody单细胞RNA测序系统分析了它们的转录组。在使用度普利尤单抗后的0至4个月内，Th2和ILC2簇基因特征下调。因此，度普利尤单抗可能通过抑制AD患者的Th2细胞和ILC2群体并改变Th2和ILC2组成来改善皮炎。
