Aberrant B Cell Receptor Signaling in Naïve B Cells from Patients with Idiopathic Pulmonary Fibrosis
| Autor: | Jennifer A C van Hulst, Jasper Rip, Odilia B. J. Corneth, Marlies S. Wijsenbeek, Peter Heukels, Rudi W. Hendriks, Stefan F H Neys |
|---|---|
| Přispěvatelé: | Pulmonary Medicine |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.drug_class QH301-705.5 B-cell receptor Naive B cell medicine.disease_cause Lymphocyte Activation Tyrosine-kinase inhibitor Article Autoimmunity Arthritis Rheumatoid 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine B cell receptor (BCR) signaling Bruton’s tyrosine kinase (BTK) medicine Agammaglobulinaemia Tyrosine Kinase nintedanib Bruton's tyrosine kinase Humans Biology (General) Protein Kinase Inhibitors B-Lymphocytes biology business.industry Phospholipase C gamma autoimmunity breakpoint cluster region General Medicine respiratory system Protein-Tyrosine Kinases Idiopathic Pulmonary Fibrosis respiratory tract diseases 030104 developmental biology chemistry Cancer research biology.protein Nintedanib idiopathic pulmonary fibrosis (IPF) business Tyrosine kinase 030215 immunology |
| Zdroj: | Cells Volume 10 Issue 6 Cells, 10(6):1321. Multidisciplinary Digital Publishing Institute (MDPI) Cells, Vol 10, Iss 1321, p 1321 (2021) |
| ISSN: | 2073-4409 |
| Popis: | Idiopathic pulmonary fibrosis (IPF) is a chronic and ultimately fatal disease in which an impaired healing response to recurrent micro-injuries is thought to lead to fibrosis. Recent findings hint at a role for B cells and autoimmunity in IPF pathogenesis. We previously reported that circulating B cells from a fraction of patients, compared with healthy controls, express increased levels of the signaling molecule Bruton’s tyrosine kinase (BTK). However, it remains unclear whether B cell receptor (BCR) signaling is altered in IPF. Here, we show that the response to BCR stimulation is enhanced in peripheral blood B cells from treatment-naïve IPF patients. We observed increased anti-immunoglobulin-induced phosphorylation of BTK and its substrate phospholipase Cγ2 (PLCγ2) in naïve but not in memory B cells of patients with IPF. In naïve B cells of IPF patients enhanced BCR signaling correlated with surface expression of transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI) but not B cell activating factor receptor (BAFFR), both of which provide pro-survival signals. Interestingly, treatment of IPF patients with nintedanib, a tyrosine kinase inhibitor with anti-fibrotic and anti-inflammatory activity, induced substantial changes in BCR signaling. These findings support the involvement of B cells in IPF pathogenesis and suggest that targeting BCR signaling has potential value as a treatment option. |
| Databáze: | OpenAIRE |
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