Immunopathogenesis Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Am J Physiol Gastrointest Liver Physiol. 2011 May;300(5):G723-8. doi: 10.1152/ajpgi.00414.2010. Epub 2011 Feb 3.
Dysregulated wound healing leads to fibrosis, whereby fibroblasts synthesize excess extracellular matrix and scarring impairs proper organ function. Although fibrotic diseases arise from diverse causes and display heterogeneous features, fibrosis commonly associates with chronic inflammation. Recent discoveries reinforce the idea that communication between fibroblasts, macrophages, and CD4 T cells integrates the processes of wound healing and host defense. Signals between macrophages and fibroblasts can exacerbate, suppress, or reverse fibrosis. Fibroblasts and macrophages are activated by T cells, but their activation also engages negative feedback loops that reduce fibrosis by restraining the immune response, particularly when the Th2 cytokine IL-13 contributes to pathology. Thus the interactions among fibroblasts, macrophages, and CD4 T cells likely play general and critical roles in initiating, perpetuating, and resolving fibrosis in both experimental and clinical conditions.
失调的伤口愈合会导致纤维化，成纤维细胞会合成过多的细胞外基质，瘢痕形成会损害器官的正常功能。尽管纤维化疾病有多种不同的病因，并表现出不同的特征，但纤维化通常与慢性炎症有关。最近的发现进一步证实了这样一种观点，即成纤维细胞、巨噬细胞和 CD4 T 细胞之间的通讯整合了伤口愈合和宿主防御的过程。巨噬细胞和成纤维细胞之间的信号可以加重、抑制或逆转纤维化。T 细胞可以激活成纤维细胞和巨噬细胞，但它们的激活也会引发负反馈回路，通过抑制免疫反应来减少纤维化，尤其是当 Th2 细胞因子 IL-13 导致病理学改变时。因此，成纤维细胞、巨噬细胞和 CD4 T 细胞之间的相互作用可能在实验和临床条件下启动、持续和解决纤维化中发挥普遍和关键的作用。
