Effective treatment of osteoarthritis (OA) remains a huge clinical challenge despite major research efforts. Different tissues and cell-types within the joint contribute to disease pathogenesis, and there is great heterogeneity between patients in terms of clinical features, genetic characteristics and responses to treatment. Inflammation and the most abundant immune cell type within the joint, macrophages, have now been recognised as possible players in disease development and progression. Here we discuss recent findings on the involvement of synovial inflammation and particularly the role of synovial macrophages in OA pathogenesis. Understanding macrophage involvement may hold the key for improved OA treatments.

IL‐12 is a potent inducer of IFN‐γ production and drives the development of Th1 cells. Human polarized Th2 cells do not express the signaling β2‐subunit of the IL‐12R and, therefore, do not signal in response to IL‐12. The question was raised as to what extent the loss of the IL‐12Rβ2 chain in Th2 cells has bearing on the stability of the human Th2 phenotype. In the present report, we show that restimulation of human fully polarized Th2 cells in the presence of IL‐12 primes for a shift towards Th0/Th1 phenotypes, accompanied by suppression of GATA‐3 expression and induction of T‐bet expression. These reversed cells are further characterized by a marked IL‐12Rβ2 chain expression and fully restored IL‐12‐inducible STAT4 activation. The IL‐12‐induced phenotypic shift proved to be stable as a subsequent restimulation in the presence of IL‐4 and in the absence of IL‐12 could not undo the accomplished changes. Identical results were obtained with cells from atopic patients, both with polyclonal Th2 cell lines and allergen‐specific Th2 cell clones. These findings suggest the possibility of restoring IL‐12 responsiveness in established Th2 cells of atopic patients by stimulation in the presence of IL‐12, and that IL‐12‐promoting immunotherapy can be beneficial for Th2‐mediated immune disorders, targeting both naive and memory effector T cells.

Biomaterials intended for in vivo applications should ideally be biodegradable to prevent their retention in the body, while avoiding the need for surgical removal. This study investigates the in vitro...

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Tolerogenic dendritic cells (tolDCs) are a promising treatment modality for diseases caused by a breach in immune tolerance, such as rheumatoid arthritis. Current medication for these diseases is directed toward symptom suppression but no real cure is available yet. TolDC-based therapy aims to restore immune tolerance in an antigen-specific manner. Here we used a mouse model to address two major questions: (i) is a maturation stimulus needed for tolDC function in vitro and in vivo and is maturation required for functioning in experimental arthritis and (ii) can tolDCs modulate CD4 + T cell responses? To answer these questions, we compared matured and immature dexamethasone/vitamin D3-generated tolDCs in vitro . Subsequently, we co-transferred these tolDCs with naïve or effector CD4 + T cells to study the characteristics of transferred T cells after 3 days with flow cytometry and Luminex multiplex assays. In addition, we tested the suppressive capabilities of tolDCs in an experimental arthritis model. We found that tolDCs cannot only modulate naïve CD4 + T cell responses as shown by fewer proliferated and activated CD4 + T cells in vivo , but also effector CD4 + T cells. In addition, Treg (CD4 + CD25 + FoxP3 + ) expansions were seen in the proliferating cell population in the presence of tolDCs. Furthermore, we show that administered tolDCs are capable to inhibit arthritis in the proteoglycan-induced arthritis model. However, a maturation stimulus is needed for tolDCs to manifest this tolerizing function in an inflammatory environment. Our data will be instrumental for optimization of future tolDC therapies for autoimmune diseases.