'Jack of all trades, master of everything' is a fair label for transforming growth factor β1 (TGF-β) - a cytokine that controls our life at many levels. In the adult organism, TGF-β1 is critical for the development and maturation of immune cells, maintains immune tolerance and homeostasis, and regulates various aspects of immune responses. Following acute tissue damages, TGF-β1 becomes a master regulator of the healing process with impacts on about every cell type involved. Divergence from the tight control of TGF-β1 actions, for instance caused by chronic injury, severe trauma, or infection can tip the balance from regulated physiological to excessive pathological repair. This condition of fibrosis is characterized by accumulation and stiffening of collagenous scar tissue which impairs organ functions to the point of failure. Fibrosis and dysregulated immune responses are also a feature of cancer, in which tumor cells escape immune control partly by manipulating TGF-β1 regulation and where immune cells are excluded from the tumor by fibrotic matrix created during the stroma 'healing' response. Despite the obvious potential of TGF-β-signalling therapies, globally targeting TGF-β1 receptor, downstream pathways, or the active growth factor have proven to be extremely difficult if not impossible in systemic treatment regimes. However, TGF-β1 binding to cell receptors requires prior activation from latent complexes that are extracellularly presented on the surface of immune cells or within the extracellular matrix. These different locations have led to some divergence in the field which is often either seen from the perspective of an immunologists or a fibrosis/matrix researcher. Despite these human boundaries, there is considerable overlap between immune and tissue repair cells with respect to latent TGF-β1 presentation and activation. Moreover, the mechanisms and proteins employed by different cells and spatiotemporal control of latent TGF-β1 activation provide specificity that is amenable to drug development. This review aims at synthesizing the knowledge on TGF-β1 extracellular activation in the immune system and in fibrosis to further stimulate cross talk between the two research communities in solving the TGF-β conundrum.

中文翻译：

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TGF-β1-纤维化和免疫力的真正转化生长因子。

“万事通，万事通”是转化生长因子β1（TGF-β）的公平标签。TGF-β是一种可在许多层面上控制我们生活的细胞因子。在成年生物中，TGF-β1对于免疫细胞的发育和成熟，维持免疫耐受性和体内平衡以及调节免疫反应的各个方面至关重要。在急性组织损伤后，TGF-β1成为愈合过程的主要调节剂，对涉及的每种细胞类型都有影响。严格控制TGF-β1的作用（例如由慢性损伤，严重创伤或感染引起）可能会导致平衡，从调节的生理状态到过度的病理修复。这种纤维化病的特征是胶原性瘢痕组织的积累和变硬，其损害器官功能至衰竭点。纤维化和免疫反应失调也是癌症的一个特征，其中肿瘤细胞部分地通过操纵TGF-β1调节而逃避了免疫控制，并且免疫细胞被基质“愈合”响应过程中产生的纤维化基质从肿瘤中排除。尽管TGF-β信号疗法具有明显的潜力，但全身性靶向TGF-β1受体，下游途径或活性生长因子已被证明非常困难，即使不是在全身治疗方案中也是如此。然而，TGF-β1与细胞受体的结合需要事先被潜在复合物激活，所述潜在复合物在免疫细胞表面上或在细胞外基质内呈现在细胞外。这些不同的位置导致了该领域的某些分歧，这通常是从免疫学家或纤维化/基质研究人员的角度来看的。尽管存在这些人类界限，但在潜在的TGF-β1呈递和激活方面，免疫细胞和组织修复细胞之间存在相当多的重叠。此外，不同细胞所采用的机制和蛋白质以及潜在的TGF-β1激活的时空控制提供了适合药物开发的特异性。这篇综述旨在综合了解免疫系统和纤维化中TGF-β1细胞外活化的知识，以进一步激发两个研究团体之间在解决TGF-β难题方面的相声。在潜在的TGF-β1呈递和激活方面，免疫细胞和组织修复细胞之间存在大量重叠。此外，不同细胞所采用的机制和蛋白质以及潜在的TGF-β1激活的时空控制提供了适合药物开发的特异性。这篇综述旨在综合了解免疫系统和纤维化中TGF-β1细胞外活化的知识，以进一步激发两个研究团体之间在解决TGF-β难题方面的相声。在潜在的TGF-β1呈递和激活方面，免疫细胞和组织修复细胞之间存在大量重叠。而且，不同细胞所采用的机制和蛋白质以及潜在的TGF-β1激活的时空控制提供了适合药物开发的特异性。这篇综述旨在综合了解免疫系统和纤维化中TGF-β1细胞外活化的知识，以进一步激发两个研究团体之间在解决TGF-β难题方面的相声。