Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
University of Edinburgh Centre for Inflammation Research, Institute for Regeneration and Repair, Edinburgh BioQuarter, Edinburgh, UK.
Nat Immunol. 2023 Sep;24(9):1423-1433. doi: 10.1038/s41590-023-01551-9. Epub 2023 Jul 20.
Fibrosis, defined by the excess deposition of structural and matricellular proteins in the extracellular space, underlies tissue dysfunction in multiple chronic diseases. Approved antifibrotics have proven modest in efficacy, and the immune compartment remains, for the most part, an untapped therapeutic opportunity. Recent single-cell analyses have interrogated human fibrotic tissues, including immune cells. These studies have revealed a conserved profile of scar-associated macrophages, which localize to the fibrotic niche and interact with mesenchymal cells that produce pathological extracellular matrix. Here we review recent advances in the understanding of the fibrotic microenvironment in human diseases, with a focus on immune cell profiles and functional immune-stromal interactions. We also discuss the key role of the immune system in mediating fibrosis regression and highlight avenues for future study to elucidate potential approaches to targeting inflammatory cells in fibrotic disorders.
纤维化是指细胞外基质中结构性和基质细胞蛋白的过度沉积，它是多种慢性疾病中组织功能障碍的基础。已批准的抗纤维化药物的疗效有限，而且免疫系统在很大程度上仍然是一个未被开发的治疗机会。最近的单细胞分析研究了包括免疫细胞在内的人类纤维化组织。这些研究揭示了一种保守的瘢痕相关巨噬细胞特征，这些细胞定位于纤维化龛位，并与产生病理性细胞外基质的间充质细胞相互作用。在这里，我们回顾了人类疾病中纤维化微环境的最新研究进展，重点介绍了免疫细胞特征和功能免疫-基质相互作用。我们还讨论了免疫系统在介导纤维化消退中的关键作用，并强调了未来研究的途径，以阐明针对纤维化疾病中炎症细胞的潜在方法。
