MRC-London Institute of Medical Sciences, Hammersmith Hospital Campus, London, U.K.
National Heart Research Institute Singapore, National Heart Centre Singapore, Singapore, Singapore.
Biochem J. 2023 Dec 13;480(23):1987-2008. doi: 10.1042/BCJ20220160.
Interleukin 11 (IL11) is an elusive member of the IL6 family of cytokines. While initially thought to be a haematopoietic and cytoprotective factor, more recent data show instead that IL11 is redundant for haematopoiesis and toxic. In this review, the reasons that led to the original misunderstandings of IL11 biology, which are now understandable, are explained with particular attention on the use of recombinant human IL11 in mice and humans. Following tissue injury, as part of an evolutionary ancient homeostatic response, IL11 is secreted from damaged mammalian cells to signal via JAK/STAT3, ERK/P90RSK, LKB1/mTOR and GSK3β/SNAI1 in autocrine and paracrine. This activates a program of mesenchymal transition of epithelial, stromal, and endothelial cells to cause inflammation, fibrosis, and stalled endogenous tissue repair, leading to organ failure. The role of IL11 signalling in cell- and organ-specific pathobiology is described, the large unknowns about IL11 biology are discussed and the promise of targeting IL11 signalling as a therapeutic approach is reviewed.
白细胞介素 11（IL11）是白细胞介素 6 家族细胞因子中难以捉摸的一员。虽然最初被认为是一种造血和细胞保护因子，但最近的数据表明，IL11 对于造血来说是多余的，而且有毒性。在这篇综述中，特别关注重组人白细胞介素 11 在小鼠和人类中的应用，解释了导致最初对白细胞介素 11 生物学的误解的原因，而这些误解现在是可以理解的。在组织损伤后，作为进化古老的体内平衡反应的一部分，IL11 从受损的哺乳动物细胞中分泌出来，通过 JAK/STAT3、ERK/P90RSK、LKB1/mTOR 和 GSK3β/SNAI1 在旁分泌和自分泌中信号传递。这激活了上皮细胞、基质细胞和内皮细胞的间充质转化程序，导致炎症、纤维化和停滞的内源性组织修复，导致器官衰竭。描述了白细胞介素 11 信号在细胞和器官特异性病理生物学中的作用，讨论了白细胞介素 11 生物学的许多未知之处，并回顾了靶向白细胞介素 11 信号作为治疗方法的前景。
