纤维化
趋化因子
成纤维细胞
病理
医学
细胞外基质
免疫学
B细胞
生物
炎症
细胞生物学
体外
抗体
生物化学
作者
Emanuel Della‐Torre,Elena Rigamonti,Cory A. Perugino,Simona Baghai Sain,Na Sun,Naoki Kaneko,Takashi Mitsui,Lucrezia Rovati,Maurilio Ponzoni,Raffaella Milani,Marco Lanzillotta,Vinay S. Mahajan,Hamid Mattoo,Ivan Molineris,Vikram Deshpande,John H. Stone,Massimo Falconi,Angelo A. Manfredi,Shiv Pillai
标识
DOI:10.1016/j.jaci.2019.07.004
摘要
Background
IgG4-related disease (IgG4-RD) is a fibroinflammatory condition marked by rapid clinical improvement after selective depletion of B lymphocytes with rituximab. This feature suggests that B cells might participate in fibrogenesis and wound healing. Objective
In the present work we aimed to demonstrate that B lymphocytes contribute directly to tissue fibrosis in patients with IgG4-RD. Methods
Total circulating CD19+ B lymphocytes, naive B cells, memory B cells, or plasmablasts from patients with IgG4-RD were cultivated with human fibroblasts. Profibrotic soluble factors and collagen production in cocultures were assessed by using ELISAs and Luminex assays. RNA sequencing and quantitative RT-PCR were used to assess fibroblast activation in the presence of B cells, as well as induction of profibrotic pathways in B-cell subsets. Relevant profibrotic and inflammatory molecules were confirmed in vitro by using functional experiments and on IgG4-RD tissue sections by using multicolor immunofluorescence studies. Results
B cells from patients with IgG4-RD (1) produced the profibrotic molecule platelet-derived growth factor B and stimulated collagen production by fibroblasts; (2) expressed enzymes implicated in extracellular matrix remodeling, such as lysyl oxidase homolog 2; (3) produced the chemotactic factors CCL4, CCL5, and CCL11; and (4) induced production of these same chemokines by activated fibroblasts. Plasmablasts expressed sets of genes implicated in fibroblast activation and proliferation and therefore represent cells with intrinsic profibrotic properties. Conclusion
We have demonstrated that B cells contribute directly to tissue fibrosis in patients with IgG4-RD. These unanticipated profibrotic properties of B lymphocytes, particularly plasmablasts, might be relevant for fibrogenesis in patients with other fibroinflammatory disorders and for wound-healing processes in physiologic conditions.
科研通智能强力驱动
Strongly Powered by AbleSci AI