Thymosin alpha 1（Tα1）独特的特性，在不同的生理和病理环境中成功地定义了它作为免疫稳态的主要调节因子。有趣的是，最近的研究还表明它对“细胞因子风暴”以及SARS-CoV-2感染者中的T细胞疲劳/激活具有缓解作用。然而，尽管在Tα1诱导T细胞反应的影响方面的认识不断增加，确认了这种多方面肽的独特特征，但它对SARS-CoV-2感染期间先天免疫的影响仍知之甚少。在这里，我们查询了外周血单个核细胞（PBMC）培养物，刺激了SARS-CoV-2，以揭示Tα1对感染早期主要细胞反应的主要细胞活动者，即单核细胞和髓样树突状细胞（mDC）的特性。从外体数据中显示COVID-19患者中炎性单核细胞和激活的mDC频率增加的情况开始，基于PBMC的实验设置在体外复制了类似的个人资料，SARS-CoV-2刺激导致CD16 +炎性单核细胞和表达CD86和HLA-DR激活标记的mDC的比例增加。有趣的是，用Tα1处理SARS-CoV-2刺激的PBMC减轻了单核细胞和mDC的炎症/激活状态，减少了促炎性介质，包括TNF-α，IL-6和IL-8的释放，同时促进了抗炎细胞因子IL-10的产生。这项研究进一步阐明了Tα1缓解COVID-19炎症病情的工作假设。此外，这些证据阐明了急性SARS-CoV-2感染涉及的炎症途径和细胞类型，这些途径和细胞类型可能成为新的免疫调节治疗方法的治疗靶点。 版权所有© 2023 Elsevier B.V.

The peculiar property of Thymosin alpha 1 (Tα1) to act as master regulator of immune homeostasis has been successfully defined in different physiological and pathological contexts ranging from cancer to infection. Interestingly, recent papers also demonstrated its mitigating effect on the "cytokine storm" as well as on the T-cell exhaustion/activation in SARS-CoV-2 infected individuals. Nevertheless, in spite of the increasing knowledge on Tα1-induced effects on T cell response confirming the distinctive features of this multifaceted peptide, little is known on its effects on innate immunity during SARS-CoV-2 infection. Here, we interrogated peripheral blood mononuclear cell (PBMC) cultures stimulated with SARS-CoV-2 to disclose Tα1 properties on the main cell players of early response to infection, namely monocytes and myeloid dendritic cells (mDC). Moving from ex vivo data showing an enhancement in the frequency of inflammatory monocytes and activated mDC in COVID-19 patients, a PBMC-based experimental setting reproduced in vitro a similar profile with an increased percentage of CD16+ inflammatory monocytes and mDC expressing CD86 and HLA-DR activation markers in response to SARS-CoV-2 stimulation. Interestingly, the treatment of SARS-CoV-2-stimulated PBMC with Tα1 dampened the inflammatory/activation status of both monocytes and mDC by reducing the release of pro-inflammatory mediators, including TNF-α, IL-6 and IL-8, while promoting the production of the anti-inflammatory cytokine IL-10. This study further clarifies the working hypothesis on Tα1 mitigating action on COVID-19 inflammatory condition. Moreover, these evidence shed light on inflammatory pathways and cell types involved in acute SARS-CoV-2 infection and likely targetable by newly immune-regulating therapeutic approaches.Copyright © 2023 Elsevier B.V. All rights reserved.