Activation of fibroblasts is a key event during normal tissue repair after injury and the dysregulated repair processes that result in organ fibrosis. To most researchers, fibroblasts are rather unremarkable spindle-shaped cells embedded in the fibrous collagen matrix of connective tissues and/or deemed useful to perform mechanistic studies with adherent cells in culture. For more than a century, fibroblasts escaped thorough classification due to the lack of specific markers and were treated as the leftovers after all other cells have been identified from a tissue sample. With novel cell lineage tracing and single cell transcriptomics tools, bona fide fibroblasts emerge as only one heterogeneous sub-population of a much larger group of partly overlapping cell types, including mesenchymal stromal cells, fibro-adipogenic progenitor cells, pericytes, and/or perivascular cells. All these cells are activated to contribute to tissue repair after injury and/or chronic inflammation. “Activation” can entail various functions, such as enhanced proliferation, migration, instruction of inflammatory cells, secretion of extracellular matrix proteins and organizing enzymes, and acquisition of a contractile myofibroblast phenotype. We provide our view on the fibroblastic cell types and activation states playing a role during physiological and pathological repair and their crosstalk with inflammatory macrophages. Inflammation and fibrosis of the articular synovium during rheumatoid arthritis and osteoarthritis are used as specific examples to discuss inflammatory fibroblast phenotypes. Ultimately, delineating the precursors and functional roles of activated fibroblastic cells will contribute to better and more specific intervention strategies to treat fibroproliferative and fibrocontractive disorders.

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成纤维细胞的炎症言语

成纤维细胞的激活是损伤后正常组织修复过程中的关键事件，以及导致器官纤维化的失调修复过程。对于大多数研究人员来说，成纤维细胞是相当不起眼的纺锤形细胞，嵌入结缔组织的纤维胶原基质中，和/或被认为可用于对培养的贴壁细胞进行机械研究。一个多世纪以来，由于缺乏特定的标记物，成纤维细胞没有被彻底分类，并且在从组织样本中识别出所有其他细胞后，它们被当作剩余物处理。凭借新颖的细胞谱系追踪和单细胞转录组学工具，真正的成纤维细胞仅作为更大的部分重叠细胞类型的一个异质亚群出现，包括间充质基质细胞、纤维脂肪祖细胞、周细胞和/或血管周围细胞。所有这些细胞都被激活以促进受伤和/或慢性炎症后的组织修复。“激活”可以带来多种功能，例如增强的增殖、迁移、炎症细胞的指导、细胞外基质蛋白和组织酶的分泌以及收缩性肌成纤维细胞表型的获得。我们提供了我们对在生理和病理修复过程中发挥作用的成纤维细胞类型和激活状态及其与炎症巨噬细胞的串扰的看法。类风湿性关节炎和骨关节炎期间关节滑膜的炎症和纤维化被用作讨论炎症成纤维细胞表型的具体例子。最终，描绘激活的成纤维细胞的前体和功能作用将有助于更好和更具体的干预策略来治疗纤维增生和纤维收缩疾病。