Adoptively Transferred in vitro-Generated Myeloid-Derived Suppressor Cells Improve T-Cell Function and Antigen-Specific Immunity after Traumatic Lung Injury.

IF 4.7 3区 医学 Q2 IMMUNOLOGY
Journal of Innate Immunity Pub Date : 2023-01-01 Epub Date: 2022-06-10 DOI:10.1159/000525088
Monika Kustermann, Prasad Dasari, Ingrid Knape, Emma Keltsch, Jianing Liu, Silvia Pflüger, Wolfram Osen, Karlheinz Holzmann, Markus Huber-Lang, Klaus-Michael Debatin, Gudrun Strauss
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引用次数: 0

Abstract

Immune reactions after trauma are characterized by immediate activation of innate immunity and simultaneously downregulation of adaptive immunity leading to a misbalanced immunohomeostasis and immunosuppression of the injured host. Therefore, the susceptibility to secondary infections is strongly increased after trauma. Immune responses are regulated by a network of immune cells influencing each other and at the same time modifying their functions dependent on the inflammatory environment. Although myeloid-derived suppressor cells (MDSCs) are initially described as T-cell suppressors, their immunomodulatory capacity after trauma is mostly undefined. Therefore, in vitro-generated MDSCs were adoptively transferred into mice after blunt chest trauma (TxT). A single MDSC treatment-induced splenic T-cell expansion decreased apoptosis sensitivity and improved proliferation in the absence of T-cell exhaustion until 2 weeks after trauma. MDSC treatment had a long-lasting effect on the genomic landscape of CD4+ T cells by upregulating primarily Th2-associated genes. Remarkably, immune-activating functions of MDSCs supported the ability of TxT mice to respond to post-traumatic secondary antigen challenge. Secondary insults were mimicked by immunizing MDSC-treated TxT mice with ovalbumin (OVA), followed by OVA restimulation in vitro. MDSC treatment significantly increased the frequency of OVA-specific T cells, enhanced their Th1/Th2 cytokine expression, and induced upregulation of cytolytic molecules finally improving OVA-specific cytotoxicity. Overall, we could show that therapeutic MDSC treatment after TxT improves post-traumatic T-cell functions, which might enable the traumatic host to counterbalance trauma-induced immunoparalysis.

过继转移体外产生的骨髓源性抑制细胞改善创伤肺损伤后的T细胞功能和抗原特异性免疫。
创伤后的免疫反应的特点是先天免疫立即激活,同时适应性免疫下调,导致受损宿主的免疫稳态和免疫抑制失调。因此,创伤后继发感染的易感性大大增加。免疫反应由免疫细胞网络调节,免疫细胞网络相互影响,同时根据炎症环境改变其功能。尽管骨髓来源的抑制细胞(MDSCs)最初被描述为T细胞抑制剂,但它们在创伤后的免疫调节能力大多尚不明确。因此,在钝性胸部创伤(TxT)后,将体外产生的MDSCs过继转移到小鼠中。单一MDSC治疗诱导的脾脏T细胞扩增降低了细胞凋亡敏感性,并在没有T细胞耗竭的情况下改善了增殖,直到创伤后2周。MDSC治疗通过主要上调Th2相关基因对CD4+T细胞的基因组景观具有持久的影响。值得注意的是,MDSCs的免疫激活功能支持TxT小鼠对创伤后二次抗原攻击的反应能力。通过用卵清蛋白(OVA)免疫MDSC处理的TxT小鼠,然后在体外再刺激OVA来模拟二次损伤。MDSC治疗显著增加了OVA特异性T细胞的频率,增强了其Th1/Th2细胞因子的表达,并诱导了细胞溶解分子的上调,最终改善了OVA特异性细胞毒性。总的来说,我们可以证明TxT后的治疗性MDSC治疗改善了创伤后T细胞的功能,这可能使创伤宿主能够平衡创伤诱导的免疫裂解。
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来源期刊
Journal of Innate Immunity
Journal of Innate Immunity 医学-免疫学
CiteScore
10.50
自引率
1.90%
发文量
35
审稿时长
7.5 months
期刊介绍: The ''Journal of Innate Immunity'' is a bimonthly journal covering all aspects within the area of innate immunity, including evolution of the immune system, molecular biology of cells involved in innate immunity, pattern recognition and signals of ‘danger’, microbial corruption, host response and inflammation, mucosal immunity, complement and coagulation, sepsis and septic shock, molecular genomics, and development of immunotherapies. The journal publishes original research articles, short communications, reviews, commentaries and letters to the editors. In addition to regular papers, some issues feature a special section with a thematic focus.
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