Interdisciplinary Graduate Program in Immunology, University of Iowa, Iowa City, IA 52242.
Department of Pathology, University of Iowa, Iowa City, IA 52242.
J Immunol. 2021 Mar 15;206(6):1171-1180. doi: 10.4049/jimmunol.2001131. Epub 2021 Jan 29.
The dysregulated sepsis-induced cytokine storm evoked during systemic infection consists of biphasic and interconnected pro- and anti-inflammatory responses. The contrasting inflammatory cytokine responses determine the severity of the septic event, lymphopenia, host survival, and the ensuing long-lasting immunoparalysis state. NK cells, because of their capacity to elaborate pro- (i.e., IFN-γ) and anti-inflammatory (i.e., IL-10) responses, exist at the inflection of sepsis-induced inflammatory responses. Thus, NK cell activity could be beneficial or detrimental during sepsis. In this study, we demonstrate that murine NK cells promote host survival during sepsis by limiting the scope and duration of the cytokine storm. Specifically, NK cell-derived IL-10, produced in response to IL-15, is relevant to clinical manifestations in septic patients and critical for survival during sepsis. This role of NK cells demonstrates that regulatory mechanisms of classical inflammatory cells are beneficial and critical for controlling systemic inflammation, a notion relevant for therapeutic interventions during dysregulated infection-induced inflammatory responses.
在全身性感染期间，失调的脓毒症引起的细胞因子风暴由双相和相互关联的促炎和抗炎反应组成。相反的炎症细胞因子反应决定了脓毒症事件的严重程度、淋巴细胞减少、宿主存活和随后的长期免疫麻痹状态。由于 NK 细胞能够产生促炎（即 IFN-γ）和抗炎（即 IL-10）反应，因此它们存在于脓毒症诱导的炎症反应的转折点。因此，NK 细胞在脓毒症期间的活动可能有益或有害。在这项研究中，我们证明了小鼠 NK 细胞通过限制细胞因子风暴的范围和持续时间来促进宿主在脓毒症中的存活。具体而言，NK 细胞衍生的 IL-10 是对 IL-15 的反应产生的，与脓毒症患者的临床表现相关，并且对脓毒症期间的存活至关重要。NK 细胞的这种作用表明，经典炎症细胞的调节机制是有益的，对于控制全身炎症至关重要，这一概念与失调的感染诱导的炎症反应期间的治疗干预有关。
