期刊
INFLAMMATION RESEARCH
卷 67, 期 2, 页码 169-177出版社
SPRINGER BASEL AG
DOI: 10.1007/s00011-017-1106-7
关键词
Classical monocytes; Non-classical monocytes; Myeloid dendritic cells; Inflammation; Chemokines; Systemic sclerosis
资金
- Portuguese national funding agency for science, research and technology: Fundacao para a Ciencia e a Tecnologia [SFRH/BD/93526/2013]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/93526/2013] Funding Source: FCT
Objective 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. Methods 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-gamma (IFN-gamma) stimulation. Results 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. Conclusions 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.
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