IntroductionThe FMS-related tyrosine kinase 3 ligand (Flt3L)/CD135 axis plays a fundamental role in proliferation and differentiation of dendritic cells (DCs). As DCs play an important role in rheumatoid arthritis (RA) immunopathology we studied in detail the Flt3L/CD135 axis in RA patients.MethodsThe levels of Flt3L in (paired) serum and synovial fluid (SF) were quantified by enzyme-link immunosorbent assay (ELISA). Expression of Flt3L and CD135 in paired peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) was quantified by fluorescence-activated cell sorting (FACS). The expression of Flt3L, CD135 and TNF-Converting Enzyme (TACE) in synovial tissues (STs) and in vitro polarized macrophages and monocyte-derived DCs (Mo-DCs) was assessed by quantitative PCR (qPCR). CD135 ST expression was evaluated by immunohistochemistry and TACE ST expression was assessed by immunofluorescence. Flt3L serum levels were assessed in RA patients treated with oral prednisolone or adalimumab.ResultsFlt3L levels in RA serum, SF and ST were significantly elevated compared to gout patients and healthy individuals (HI). RA SF monocytes, natural killer cells and DCs expressed high levels of Flt3L and CD135 compared to HI. RA ST CD68+ and CD163+ macrophages, CD55+ fibroblast-like synoviocytes (FLS), CD31+ endothelial cells or infiltrating monocytes and CD19+ B cells co-expressed TACE. IFN-γ-differentiated macrophages expressed higher levels of Flt3L compared to other polarized macrophages. Importantly, Flt3L serum levels were reduced by effective therapy.ConclusionsThe Flt3L/CD135 axis is active in RA patients and is responsive to both prednisolone and adalimumab treatment. Conceivably, this ligand receptor pair represents a novel therapeutic target.

Spondyloarthritis (SpA) is a family of chronic inflammatory diseases, being the most prevalent ankylosing spondylitis (AS) and psoriatic arthritis (PsA). These diseases share genetic, clinical and immunological features, such as the implication of human leukocyte antigen (HLA) class I molecule 27 (HLA-B27), the inflammation of peripheral, spine and sacroiliac joints and the presence of extra-articular manifestations (psoriasis, anterior uveitis, enthesitis and inflammatory bowel disease). Monocytes and macrophages are essential cells of the innate immune system and are the first line of defence against external agents. In rheumatic diseases including SpA, the frequency and phenotypic and functional characteristics of both cell types are deregulated and are involved in the pathogenesis of these diseases. In fact, monocytes and macrophages play key roles in the inflammatory processes characteristics of SpA. The aim of this review is analysing the characteristics and functional roles of monocytes and macrophages in these diseases, as well as the impact of different current therapies on these cell types.