OBJECTIVES: Although myeloid-derived suppressor cells (MDSCs) have been linked to T cell tolerance, their role in @entity309 ( @entity309 ) remains elusive. Here we investigate the potential association of MDSCs with the disease pathogenesis using a preclinical model of @entity309 and specimen collected from @entity1 with @entity309 . METHODS: The frequency of MDSCs in blood, lymphoid tissues, inflamed paws or synovial fluid and their association with disease severity, tissue @entity32 and the levels of pathogenic T helper (Th) 17 cells were examined in arthritic @entity19 or in @entity1 with @entity309 (n=35) and @entity571 (n=15). The MDSCs in arthritic @entity19 were also characterised for their phenotype, @entity32 status, T cell suppressive activity and their capacity of pro-Th17 cell differentiation. The involvement of MDSCs in the disease pathology and a Th17 response was examined by adoptive transfer or antibody depletion of MDSCs in arthritic @entity19 or by coculturing @entity19 or @entity1 MDSCs with na  ve CD4+ T cells under Th17-polarising conditions. RESULTS: MDSCs significantly expanded in arthritic @entity19 and in @entity1 with @entity309 , which correlated positively with disease severity and an inflammatory Th17 response. While displaying T cell suppressive activity, MDSCs from arthritic @entity19 produced high levels of inflammatory cytokines (eg, @entity635 , @entity637 ). @entity19 and @entity1 MDSCs promoted Th17 cell polarisation ex vivo. Transfer of MDSCs facilitated disease progression, whereas their elimination in arthritic @entity19 @entity66 concomitant with reduction of @entity636 /Th17 cells. CONCLUSIONS: Our studies suggest that proinflammatory MDSCs with their capacity to drive Th17 cell differentiation may be a critical pathogenic factor in @entity625 .

Myeloid-derived suppressor cells have a proinflammatory role in the pathogenesis of XXXX .

@entity1 :: ('9606', 'Species') :: ['patients', 'human'] @entity32 :: ('MESH:D007249', 'Disease') :: ['inflammation'] @entity571 :: ('MESH:D010003', 'Disease') :: ['osteoarthritis'] @entity66 :: ('MESH:D004194', 'Disease') :: ['ameliorated disease symptoms'] @entity625 :: ('MESH:D001168', 'Disease') :: ['autoimmune arthritis'] @entity19 :: ('10090', 'Species') :: ['mice', 'Mouse', 'mouse'] @entity635 :: ('16176(Tax:10090)', 'Gene') :: ['interleukin (IL)-1b'] @entity636 :: ('16171(Tax:10090)', 'Gene') :: ['IL-17A'] @entity637 :: ('21926(Tax:10090)', 'Gene') :: ['TNF-a'] @entity309 :: ('MESH:D001172', 'Disease') :: ['autoimmune rheumatoid arthritis', 'RA']
@entity625 :: (MESH:D001168,Disease) :: ['autoimmune arthritis']
