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In a companion article to this study,1 the successful programming of a JAWSII dendritic cell ( DC) line's antigen uptake and processing was demonstrated based on pre-treatment of DCs with a specific 'cocktail' of select chemokines. Chemokine pre-treatment modulated cytokine production before and after DC maturation [by lipopolysaccharide (LPS)]. After DC maturation, it induced an antigen uptake and processing capacity at levels 36% and 82% higher than in immature DCs, respectively. Such programming proffers a potential new approach to enhance vaccine efficiency. Unfortunately, simply enhancing antigen uptake does not guarantee the desired activation and proliferation of lymphocytes, e.g. CD4+ T cells. In this study, phenotype changes and antigen presentation capacity of chemokine pre-treated murine bone marrow-derived DCs were examined in long-term co-culture with antigen-specific CD4+ T cells to quantify how chemokine pre-treatment may impact the adaptive immune response. When a model antigen, ovalbumin ( OVA), was added after intentional LPS maturation of chemokine-treated DCs, OVA-biased CD4+ T-cell proliferation was initiated from ~ 100% more undivided naive T cells as compared to DCs treated only with LPS. Secretion of the cytokines interferon-γ, interleukin-1β, interleukin-2 and interleukin-10 in the CD4+ T cell : DC co-culture (with or without chemokine pre-treatment) were essentially the same. Chemokine programming of DCs with a 7 : 3 ratio of CCL3 : CCL19 followed by LPS treatment maintained partial immature phenotypes of DCs, as indicated by surface marker ( CD80 and CD86) expression over time. Results here and in our companion paper suggest that chemokine programming of DCs may provide a novel immunotherapy strategy to obviate the natural endocytosis limit of DC antigen uptake, thus potentially increasing DC-based vaccine efficiency. [ABSTRACT FROM AUTHOR]

Chronic inflammation of the adipose tissue (AT) is a critical component of obesity-induced insulin resistance and type 2 diabetes. Adipose tissue immune cells, including AT macrophages (ATMs), AT dendritic cells (ATDCs), and T cells, are dynamically regulated by obesity and participate in obesity-induced inflammation. Among AT resident immune cells, ATDCs are master immune regulators and engage in crosstalk with various immune cells to initiate and regulate immune responses. However, due to confounding markers and lack of animal models, their exact role and contribution to the initiation and maintenance of AT inflammation and insulin resistance have not been clearly elucidated. This paper reviews the current understanding of ATDCs and their role in obesity-induced AT inflammation. We also provide the potential mechanisms by which ATDCs regulate AT inflammation and insulin resistance in obesity. Finally, this review offers perspectives on ways to better dissect the distinct functions and contributions of ATDCs to obesity. [ABSTRACT FROM AUTHOR]

Background: In the liver, several types of cells are involved in antigen presentation. In addition to myeloid antigen presenters such as Kupffer cells or dendritic cells, liver sinusoidal endothelial cells (LSECs) can express MHC and costimulatory molecules and are capable of presenting antigens. Objective: Targeting LSECs could be of therapeutical use in treatment of autoimmune disorders. Being in permanent contact with blood from systemic and portal circulations, LSEC is an important player in taking up and eliminating blood-borne soluble antigens and in determining the nature of the immune response such antigens stimulate. Generally, LSECs promote tolerance in both MHC I and II systems. Naïve CD4+ T-cells primed by LSECs using the MHC class II pathway can differentiate into two types of regulatory T-cells (Tregs): one expressing Forkhead-Box-Protein P3 (FoxP3) and the other lacking this transcription factor. These peripherally induced Tregs are important in maintaining tolerance to antigens that are not presented in thymus. This tolerogenic effect of LSECs has been rather controversial because they constitutively carry low levels of MHC II, but the exposure of MHC class II molecules may rise under the influence of inflammatory cytokines. Material and methods: Data analysis of scientific papers regarding the fascinating roles of liver sinusoidal endothelial cells in the immunologic microenvironment of the liver and the prospects of using these mechanisms therapeutically. Results: There are encouraging studies which used this technique and succeeded in curing experimental autoimmune encephalomyelitis in mice so we consider that this topic should be furthermore researched. Conclusions: LSECs possess the most potent endocytic capacity in the body; therefore, developing special nanoparticles which can deliver autoantigen peptides only to LSECs could be an efficient way to induce tolerance for the autoantigen. [ABSTRACT FROM AUTHOR]