Abstract
ObjectiveTo 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.MethodsSpontaneous 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.ResultsThe 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.ConclusionsThese 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.
Highlights
Systemic sclerosis (SSc) is a chronic connective tissue disease, characterized by vascular abnormalities and Department of Rheumatology, Coimbra University Hospital Center, Coimbra, PortugalFaculty of Medicine, University of Coimbra, Coimbra, PortugalFlow Cytometry Unit, Clinical Pathology Service, Coimbra University Hospital Center, Praceta Prof
We evaluated the production of CXCL10, CCL4, CXCL8 and IL-6 in circulating classical monocytes, non-classical monocytes and myeloid DCs in patients with diffuse cutaneous and limited cutaneous SSc and compared this to that observed in healthy counterparts
SSc is a complex disease with heterogeneous clinical features and disease severity, corresponding to the extent of skin fibrosis and internal organ involvement, as a consequence of excessive collagen production and accumulation
Summary
Systemic sclerosis (SSc) is a chronic connective tissue disease, characterized by vascular abnormalities and Department of Rheumatology, Coimbra University Hospital Center, Coimbra, Portugal. Faculty of Medicine, University of Coimbra, Coimbra, Portugal. Flow Cytometry Unit, Clinical Pathology Service, Coimbra University Hospital Center, Praceta Prof. 3° piso, 30001‐301 Coimbra, Portugal immunological disturbances followed by progressive fibrosis of the skin and internal organs. SSc is recognized as the most severe connective tissue disorder and the most resistant to therapy, being associated with the highest case-specific mortality among rheumatic diseases. The etiology of SSc is largely unknown and its pathogenesis is complex and poorly understood [1, 2]
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