Jiménez-Cortegana Carlos , Palomares Francisca , Alba Gonzalo, Santa-María Consuelo , de la Cruz-Merino Luis , Sánchez-Margalet Victor , López-Enríquez Soledad Frontiers in Immunology 14,2024, doi.org=10.3389/fimmu.2023.1321051

Dendritic cells (DCs) are antigen presenting cells that link innate and adaptive immunity. DCs have been historically considered as the most effective and potent cell population to capture, process and present antigens to activate naïve T cells and originate favorable immune responses in many diseases, such as cancer. However, in the last decades, it has been observed that DCs not only promote beneficial responses, but also drive the initiation and progression of some pathologies, including inflammatory bowel disease (IBD). In line with those notions, different therapeutic approaches have been tested to enhance or impair the concentration and role of the different DC subsets. The blockade of inhibitory pathways to promote DCs or DC-based vaccines have been successfully assessed in cancer, whereas the targeting of DCs to inhibit their functionality has proved to be favorable in IBD. In this review, we (a) described the general role of DCs, (b) explained the DC subsets and their role in immunogenicity, (c) analyzed the role of DCs in cancer and therapeutic approaches to promote immunogenic DCs and (d) analyzed the role of DCs in IBD and therapeutic approaches to reduced DC-induced inflammation. Therefore, we aimed to highlight the “yin-yang” role of DCs to improve the understand of this type of cells in disease progression.

Shin-ichiro Takeda ¹, Toru Sato, Tatsuro Katsuno, Tomoo Nakagawa, Yoshiko Noguchi, Osamu Yokosuka, Yasushi Saito, Dig Dis Sci. 2010 Jul;55(7):1886-95.

We found high expressions of alpha4 integrin and CX(3)CR1 on monocytes in patients with active UC, known to promote the extravasation of CD14(+)CD16(+) monocytes into the mucosa. GMA effectively depletes CD14(+)CD16(+) monocytes and concomitantly increases CD14(hi)CD16(-)CCR2(low) « immature » monocytes; thus GMA was associated with the emergence of less inflammatory monocyte phenotype in circulation.

https://pubmed.ncbi.nlm.nih.gov/19908144/

Yuko Iwakami,Atsushi Sakuraba,Toshiro Sato,Yasuhiro Takada,Motoko Izumiya,Hitoshi Ichikawa,Toshifumi Hibi Ther Apher Dial 13, 2 (2009); 138-146

The aim of this study was to elucidate the molecular mechanisms responsible for the therapeutic effects of granulocyte and monocyte adsorption apheresis (GMA). We investigated the alterations in circulating monocyte subsets and monocyte-derived dendritic cell (moDC) function after GMA therapy in ulcerative colitis (UC) patients. Eighteen patients with UC were enrolled: 14 patients were responders, and 4 patients were non-responders. Peripheral venous blood was obtained within 5 min before and 5 min after GMA therapy. Flow cytometric analysis for monocyte markers (CD14/CD16) was then performed. Monocyte-derived dendritic cells were obtained and alterations in their phenotype were analyzed by flow cytometry. Their function was also analyzed in a mixed lymphocyte reaction assay between allo-naïve T lymphocytes. Flow cytometric analysis for intracellular interferon (IFN)-γ (T-helper 1 cells) and interleukin (IL)-4 (T-helper 2 cells) was then performed for the stimulated T lymphocytes. In patients who responded to GMA, the average numbers of monocytes, especially CD16⁺ monocytes, were significantly decreased after therapy (P < 0.05). In responders, post-GMA moDCs expressed significantly lower CD80 and B7-DC, which are one of the stimulation and maturation markers of dendritic cells, compared to pre-GMA moDCs. CD83, CD86 and human leukocytcde antigen-DR also showed a tendency to decrease. In responders, naïve T lymphocytes stimulated with post-GMA moDCs produced significantly less IFN-γ and IL-4 compared to those stimulated with pre-GMA moDCs. The results of our study show that some of the immunosuppressive effects of GMA therapy may be associated with the modulation of monocyte subsets and moDC function.

https://pubmed.ncbi.nlm.nih.gov/19379153/

https://onlinelibrary.wiley.com/doi/10.1111/j.1744-9987.2009.00668.x