Increased frequencies of circulating CXCL10-, CXCL8- and CCL4-producing monocytes and Siglec-3-expressing myeloid dendritic cells in systemic sclerosis patients
Copyright policy )Increased frequencies of circulating CXCL10-, CXCL8- and CCL4-producing monocytes and Siglec-3-expressing myeloid dendritic cells in systemic sclerosis patients
To investigate the ex vivo pro-inflammatory properties of classical and non-classical monocytes as well as myeloid dendritic cells (mDCs) in systemic sclerosis (SSc) patients.Spontaneous production of CXCL10, CCL4, CXCL8 and IL-6 was intracellularly evaluated in classical, non-classical monocytes and Siglec-3-expressing mDCs from peripheral blood of SSc patients and healthy controls (HC) through flow cytometry. In addition, production of these cytokines was determined upon toll-like receptor (TLR) 4 plus Interferon-γ (IFN-γ) stimulation.The frequency of non-classical monocytes spontaneously producing CXCL10 was increased in both limited (lcSSc) and diffuse cutaneous (dcSSC) subsets of SSc patients and CCL4 was augmented in dcSSc patients. The proportion of CCL4-producing mDCs was also elevated in dcSSc patients and the percentage of mDCS producing CXCL10 only in lcSSc patients. Upon stimulation, the frequency of non-classical monocytes expressing CXCL8 was increased in both patient groups and mDCs expressing CXCL8 only in lcSSc. Moreover, these parameters in unsupervised clustering analysis identify a subset of patients which are characterized by lung fibrosis and reduced pulmonary function.These data point towards a role of activated non-classical monocytes and mDCs producing enhanced levels of proinflammatory cytokines in SSc, potentially contributing to lung fibrosis.
- University of Aveiro Portugal
- Hospitais da Universidade de Coimbra Portugal
- University of Aveiro Portugal
- University of Coimbra Portugal
- Utrecht University Netherlands
Adult, Male, Sialic Acid Binding Ig-like Lectin 1, Pulmonary Fibrosis, Immunology, Myeloid dendritic cells, Non-classical monocytes, Scleroderma, Systemic/metabolism, Monocytes, Dendrites/metabolism, Cytokines/biosynthesis, Pulmonary Fibrosis/metabolism, Monocytes/metabolism, Journal Article, Humans, Myeloid Cells, Chemokine CCL4, Aged, Inflammation, Pharmacology, Classical monocytes, Sialic Acid Binding Ig-like Lectin 1/metabolism, Scleroderma, Systemic, Chemokine CXCL10/metabolism, Interleukin-8, Myeloid Cells/metabolism, Chemokine CCL4/metabolism, Dendrites, Middle Aged, Original Research Paper, Chemokine CXCL10, Toll-Like Receptor 4, Toll-Like Receptor 4/metabolism, Interleukin-8/metabolism, Systemic sclerosis, Cytokines, Female, Interferons, Chemokines, Interferons/metabolism
Adult, Male, Sialic Acid Binding Ig-like Lectin 1, Pulmonary Fibrosis, Immunology, Myeloid dendritic cells, Non-classical monocytes, Scleroderma, Systemic/metabolism, Monocytes, Dendrites/metabolism, Cytokines/biosynthesis, Pulmonary Fibrosis/metabolism, Monocytes/metabolism, Journal Article, Humans, Myeloid Cells, Chemokine CCL4, Aged, Inflammation, Pharmacology, Classical monocytes, Sialic Acid Binding Ig-like Lectin 1/metabolism, Scleroderma, Systemic, Chemokine CXCL10/metabolism, Interleukin-8, Myeloid Cells/metabolism, Chemokine CCL4/metabolism, Dendrites, Middle Aged, Original Research Paper, Chemokine CXCL10, Toll-Like Receptor 4, Toll-Like Receptor 4/metabolism, Interleukin-8/metabolism, Systemic sclerosis, Cytokines, Female, Interferons, Chemokines, Interferons/metabolism
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