Center for Musculoskeletal Research, University of Rochester Medical Center, Rochester, NY, United States.
Department of Orthopaedics and Rehabilitation, University of Rochester Medical Center, Rochester, NY, United States.
Front Immunol. 2021 May 17;12:678515. doi: 10.3389/fimmu.2021.678515. eCollection 2021.
Innate and adaptive immune responses against pathogens are known to be carefully orchestrated by specific cytokines that initiate and down regulate immune cell functions from the initial infection through tissue repair and homeostasis. However, some cytokines, including interleukin-27, are expressed at multiple phases of the infection, such that their pro and anti-inflammatory functions have been difficult to interpret. As elucidation of specific cytokine functions throughout infection is central to our understanding of protective susceptible immunity and return to homeostasis prolonged inflammation leading to septic shock, here we review the literature on IL-27 signaling and the various functions of this heterodimeric ligand member of the IL-12 cytokine family. Canonically, IL-27 is produced by antigen-presenting cells, and is thought of as an immunostimulatory cytokine due to its capacity to induce Th1 differentiation. However, many studies have also identified various immunosuppressive effects of IL-27 signaling, including suppression of Th17 differentiation and induction of co-inhibitory receptors on T cells. Thus, the exact role of IL-27 in the context of infectious diseases remains a topic of debate and active research. Additionally, as recent interest has focused on clinical management of acute chronic infections, and life-threatening "cytokine storm" from sepsis, we propose a hypothetical model to explain the biphasic role of IL-27 during the early and late phases of immune responses to reconcile its known pro and anti-inflammatory functions, which could be therapeutically regulated to improve patient outcomes of infection.
先天免疫和适应性免疫反应被认为是由特定的细胞因子精心协调的，这些细胞因子从初始感染到组织修复和内稳态，启动并下调免疫细胞的功能。然而，一些细胞因子，包括白细胞介素-27，在感染的多个阶段表达，因此它们的促炎和抗炎功能一直难以解释。由于阐明感染过程中特定细胞因子的功能对于我们理解保护性和易感性免疫以及恢复内稳态与延长炎症导致败血症性休克至关重要，因此，我们在这里回顾了关于白细胞介素-27 信号及其作为白细胞介素-12 细胞因子家族成员的异二聚配体的各种功能的文献。通常，白细胞介素-27 由抗原呈递细胞产生，由于其诱导 Th1 分化的能力，被认为是一种免疫刺激细胞因子。然而，许多研究也发现了白细胞介素-27 信号的各种免疫抑制作用，包括抑制 Th17 分化和诱导 T 细胞上的共抑制受体。因此，白细胞介素-27 在传染病背景下的确切作用仍然是一个有争议的话题，也是一个活跃的研究领域。此外，由于最近的兴趣集中在急性和慢性感染的临床管理以及败血症导致的危及生命的“细胞因子风暴”上，我们提出了一个假设模型，以解释白细胞介素-27 在免疫反应的早期和晚期的双相作用，以协调其已知的促炎和抗炎功能，这可以通过治疗调节来改善感染患者的预后。
