The chemokine CCL1 triggers an AMFR-SPRY1 pathway that promotes differentiation of lung fibroblasts into myofibroblasts and drives pulmonary fibrosis
| Autor: | Bing Cui, Fang Hua, Jiao-jiao Yu, Yang Xiao, Shuang Shang, Pingping Li, Xiaoxi Lv, Xiaowei Zhang, Zhi-guang Zhou, Yun-xuan Li, Zhuo-Wei Hu, Jun Yan, Jin-mei Yu, Shan-Shan Liu, Chang Liu, Feng Wang, Ke Li |
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| Rok vydání: | 2021 |
| Předmět: |
Pulmonary Fibrosis
Immunology Inflammation CCL1 Lung injury CCR8 Biology Chemokine CCL1 Mice Chemokine receptor Pulmonary fibrosis medicine Animals Humans Immunology and Allergy Myofibroblasts Adaptor Proteins Signal Transducing medicine.diagnostic_test Membrane Proteins Cell Differentiation Fibroblasts Phosphoproteins medicine.disease Receptors Autocrine Motility Factor Bronchoalveolar lavage Infectious Diseases Cancer research medicine.symptom Signal Transduction |
| Zdroj: | Immunity. 54:2433-2435 |
| ISSN: | 1074-7613 |
| DOI: | 10.1016/j.immuni.2021.09.009 |
| Popis: | Summary Recruitment of immune cells to the site of inflammation by the chemokine CCL1 is important in the pathology of inflammatory diseases. Here, we examined the role of CCL1 in pulmonary fibrosis (PF). Bronchoalveolar lavage fluid from PF mouse models contained high amounts of CCL1, as did lung biopsies from PF patients. Immunofluorescence analyses revealed that alveolar macrophages and CD4+ T cells were major producers of CCL1 and targeted deletion of Ccl1 in these cells blunted pathology. Deletion of the CCL1 receptor Ccr8 in fibroblasts limited migration, but not activation, in response to CCL1. Mass spectrometry analyses of CCL1 complexes identified AMFR as a CCL1 receptor, and deletion of Amfr impaired fibroblast activation. Mechanistically, CCL1 binding triggered ubiquitination of the ERK inhibitor Spry1 by AMFR, thus activating Ras-mediated profibrotic protein synthesis. Antibody blockade of CCL1 ameliorated PF pathology, supporting the therapeutic potential of targeting this pathway for treating fibroproliferative lung diseases. |
| Databáze: | OpenAIRE |
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