Suppression of dendritic cell maturation and T cell proliferation by synovial fluid myeloid cells from mice with autoimmune arthritis.

摘要: Granulocytes (mainly neutrophils) are abundantly present in the synovial fluid (SF) of inflamed joints patients with rheumatoid arthritis (RA) (1,2), and these cells also constitute a major population joint-infiltrating murine models RA including proteoglycan (PG)-induced (PGIA) (3–7). Neutrophils can inflict considerable damage to joint tissues via secretion proteinases, reactive oxygen species (ROS), cytokines, chemoattractants (8). In addition, they interact other cell types such as dendritic (DCs) that arthritic (9,10). Effects neutrophils on joint-resident DCs, which migrate draining lymph nodes (JDLNs) (11) may joint-derived autoantigens (autoAgs) T cells, could be importance. both human systems, activated have been shown induce maturation DCs cell-cell contact DC-activating cytokines (12–14). Such an interaction between increase autoimmune response through enhancement migration their capacity autoAgs JDLNs. Conversely, if suppressive subsets or myeloid lineage joint, prevent spreading by inhibiting thus limiting activation autoreactive JDLNs. A recently described population, termed myeloid-derived suppressor (MDSCs), has implicated suppression activation. MDSCs heterogeneous group belong CD11b+ (15). First identified cancer tumor-bearing animals, were later found enriched under conditions infection, organ transplantation, autoimmunity (reviewed (16)). mice, two populations (Ly6-GhiLy6-Cint/lo Ly6-Gneg/loLy6-Chi) distinguished (15,17). Morphologically, Ly6-GhiLy6-Cint/lo subset resembles granulocytes (neutrophils), whereas Ly6-ChiLy6-Gneg/lo consists monocyte-like cells. The activities mechanistically linked upregulation arginase 1, inducible nitric oxide (NO) synthase (iNOS), production ROS (16,18–20). Although presence large granulocytic PGIA long known, possibility activating (thus potentially enhancing autoimmunity) acting suppressing autoimmunity), not considered. Therefore, primary goal this study was determine whether SF (and spleen) mice contained promote suppress DC maturation, potential affect DC-mediated