期刊
EUROPEAN JOURNAL OF IMMUNOLOGY
卷 45, 期 5, 页码 1414-1425出版社
WILEY
DOI: 10.1002/eji.201445100
关键词
LFA-1; Monocyte; Rheumatoid arthritis; Th17; TLR-2
类别
资金
- Swiss National Science Foundation (SNF) [3100A0-100188/1]
- Fundacao para a Ciencia e a Tecnologia [PDTC/SAU-MII/69796/2006]
- Krebsliga Beider Basel [15-2012]
- SNF [PP00P3-13369]
- Department of Surgery of Basel University Hospital (Basel, CH)
Among human peripheral blood (PB) monocyte (Mo) subsets, the classical CD14(++)CD16(-) (cMo) and intermediate CD14(++)CD16(+) (iMo) Mos are known to activate pathogenic Th17 responses, whereas the impact of nonclassical CD14(+)CD16(++) Mo (nMo) on T-cell activation has been largely neglected. The aim of this study was to obtain new mechanistic insights on the capacity of Mo subsets from healthy donors (HDs) to activate IL-17(+) T-cell responses in vitro, and assess whether this function was maintained or lost in states of chronic inflammation. When cocultured with autologous CD4(+) T cells in the absence of TLR-2/NOD2 agonists, PB nMos from HDs were more efficient stimulators of IL-17-producing T cells, as compared to cMo. These results could not be explained by differences in Mo lifespan and cytokine profiles. Notably, however, the blocking of LFA-1/ICAM-1 interaction resulted in a significant increase in the percentage of IL-17(+) T cells expanded in nMo/T-cell cocultures. As compared to HD, PB Mo subsets of patients with rheumatoid arthritis were hampered in their T-cell stimulatory capacity. Our new insights highlight the role of Mo subsets in modulating inflammatory T-cell responses and suggest that nMo could become a critical therapeutic target against IL-17-mediated inflammatory diseases.
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