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The chemokine CCL1 triggers an AMFR-SPRY1 pathway that promotes differentiation of lung fibroblasts into myofibroblasts and drives pulmonary fibrosis
- Source :
- Immunity. 54:2433-2435
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 10747613
- Volume :
- 54
- Database :
- OpenAIRE
- Journal :
- Immunity
- Accession number :
- edsair.doi.dedup.....8bad8d5d340d83ba8caa6849e9eb7577