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Cells
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Dendritic Cells in Immunity and Inflammation
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Dendritic Cells in Immunity and Inflammation

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Immunology".

Deadline for manuscript submissions: closed (31 July 2020) | Viewed by 19024

Special Issue Editor

Dr. Gaetano Finocchiaro

E-Mail Website
Guest Editor
Unitof Molecular Neuro-Oncology, Fondazione IRCCS Istituto Neurologico C. Besta, 20133 Milan, Italy
Interests: brain cancer; gliomas; cancer immunotherapy; cancer genetics

Special Issue Information

Dear Colleagues,

Since their discovery in 1973 by the Nobel laureate Ralph Steinman and his colleague Zanvil Cohn, more than 50,000 papers have been published on dendritic cells (DCs), testifying to their absolute relevance in the landscape of immunity. DCs are truly major players in the immune system and particularly in adaptive immunity. The progress in the understanding of their biology has been impressive and in close relationship with the definition of their role in diverse human diseases. The focus of this series would be exactly on this, covering disease mechanisms that are of completely different origins, like cancer, infections or autoimmune disorders. Indeed, the attempt to modulate DC functions in opposite directions well illustrates the extraordinary therapeutic potential and the biological “flexibility” of these cells. In autoimmune disorders like lupus erythematosus or multiple sclerosis (although the term of immune-mediated disorder is probably more acceptable for multiple sclerosis), the generation of tolerogenic DC is actively pursued. Recent data also raised the intriguing possibility that DCs play a role in the evolution of degenerative diseases like amyotrophic lateral sclerosis. In cancer, by contrast, DC alerting and activation against nonself neoantigens is the strategy that has been under scrutiny in a number of clinical studies for several years. In this context, the interaction of DCs with T lymphocytes and natural killer cells is of paramount importance. Also important are the recent acquisitions in their classification, ways of purifications, as well as the innovations in their stimulation/activation for therapeutic purposes.

Finally, as the immunotherapy field is moving really fast, a new wave of interactions can be envisioned between DCs and the adoptive transfer of T cells, including chimeric antigen receptors, looking for possible synergies.

In this Special Issue of Cells, we invite contributions in the form of original research articles, reviews, or shorter perspective articles on all aspects related to dendritic cells and the themes above.

Dr. Gaetano Finocchiaro
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • dendritic cells and T cells
  • dendritic cells and NK cells
  • tolerogenic DC
  • dendritic cells and cancer
  • dendritic cells and immune-mediated diseases
  • adoptive immunotherapy

Published Papers (5 papers)

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Research

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12 pages, 3102 KiB  
Article
Ligation of MHC Class II Induces PKC-Dependent Clathrin-Mediated Endocytosis of MHC Class II
by Kento Masaki, Yuhji Hiraki, Hiroka Onishi, Yuka Satoh, Paul A. Roche, Satoshi Tanaka and Kazuyuki Furuta
Cells 2020, 9(8), 1810; https://doi.org/10.3390/cells9081810 - 30 Jul 2020
Cited by 5 | Viewed by 3130
Abstract
In addition to antigen presentation to CD4+ T cells, aggregation of cell surface major histocompatibility complex class II (MHC-II) molecules induces signal transduction in antigen presenting cells that regulate cellular functions. We previously reported that crosslinking of MHC-II induced the endocytosis of [...] Read more.
In addition to antigen presentation to CD4+ T cells, aggregation of cell surface major histocompatibility complex class II (MHC-II) molecules induces signal transduction in antigen presenting cells that regulate cellular functions. We previously reported that crosslinking of MHC-II induced the endocytosis of MHC-II, which was associated with decreased surface expression levels in murine dendritic cells (DCs) and resulted in impaired activation of CD4+ T cells. However, the downstream signal that induces MHC-II endocytosis remains to be elucidated. In this study, we found that the crosslinking of MHC-II induced intracellular Ca2+ mobilization, which was necessary for crosslinking-induced MHC-II endocytosis. We also found that these events were suppressed by inhibitors of Syk and phospholipase C (PLC). Treatments with a phorbol ester promoted MHC-II endocytosis, whereas inhibitors of protein kinase C (PKC) suppressed crosslinking-induced endocytosis of MHC-II. These results suggest that PKC could be involved in this process. Furthermore, crosslinking-induced MHC-II endocytosis was suppressed by inhibitors of clathrin-dependent endocytosis. Our results indicate that the crosslinking of MHC-II could stimulate Ca2+ mobilization and induce the clathrin-dependent endocytosis of MHC-II in murine DCs. Full article
(This article belongs to the Special Issue Dendritic Cells in Immunity and Inflammation)
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14 pages, 2031 KiB  
Article
Cetuximab and IL-15 Promote NK and Dendritic Cell Activation In Vitro in Triple Negative Breast Cancer
by Estefanía Paula Juliá, José Mordoh and Estrella Mariel Levy
Cells 2020, 9(7), 1573; https://doi.org/10.3390/cells9071573 - 28 Jun 2020
Cited by 16 | Viewed by 3044
Abstract
Triple Negative Breast Cancer (TNBC) treatment is still challenging, and immunotherapy is a potential approach in this tumor subtype. Cetuximab is an IgG1 monoclonal antibody (mAb) directed against Epidermic Growth Factor Receptor (EGFR), a protein overexpressed in a subgroup of TNBC patients and [...] Read more.
Triple Negative Breast Cancer (TNBC) treatment is still challenging, and immunotherapy is a potential approach in this tumor subtype. Cetuximab is an IgG1 monoclonal antibody (mAb) directed against Epidermic Growth Factor Receptor (EGFR), a protein overexpressed in a subgroup of TNBC patients and associated with poor prognosis. Previously, we demonstrated in vitro that Cetuximab triggers Ab-dependent cell cytotoxicity against TNBC cells. In this study, using co-cultures including TNBC cells, and NK and Dendritic Cells (DCs) from healthy donors, we studied the effect of Cetuximab-activated NK cells on DC function. Given that we already demonstrated that TNBC has an immunosuppressive effect on NK cells, we also tested Cetuximab combination with IL-15. We determined that Cetuximab opsonization of TNBC cells increased IFN-γ and TNF-α production by NK cells co-cultured with DCs. Moreover, we showed that NK cells activated by TNBC cells opsonized with Cetuximab promoted tumor material uptake and maturation of DCs, as well as their ability to produce IL-12. Furthermore, the stimulation with IL-15 increased the activation of NK cells and the maturation of DCs. These results suggest that IL-15 may enhance the efficacy of Cetuximab in the treatment of TNBC by promoting activation of both NK cells and DCs. Full article
(This article belongs to the Special Issue Dendritic Cells in Immunity and Inflammation)
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12 pages, 3309 KiB  
Communication
TLR2 and Dectin-1 Signaling in Mouse Hematopoietic Stem and Progenitor Cells Impacts the Ability of the Antigen Presenting Cells They Produce to Activate CD4 T Cells
by Alba Martínez, Cristina Bono, Daniel Gozalbo, Helen S. Goodridge, M. Luisa Gil and Alberto Yáñez
Cells 2020, 9(5), 1317; https://doi.org/10.3390/cells9051317 - 25 May 2020
Cited by 17 | Viewed by 3215
Abstract
Microbial recognition by pattern recognition receptors (PRRs) expressed on hematopoietic stem and progenitor cells (HSPCs) not only activates myelopoiesis but also programs the function of the monocytes and macrophages they produce. For instance, changes in HSPC programming modify the ability of macrophages derived [...] Read more.
Microbial recognition by pattern recognition receptors (PRRs) expressed on hematopoietic stem and progenitor cells (HSPCs) not only activates myelopoiesis but also programs the function of the monocytes and macrophages they produce. For instance, changes in HSPC programming modify the ability of macrophages derived from them to produce inflammatory cytokines. While HSPCs exposed to a TLR2 agonist give rise to tolerized macrophages (lower proinflammatory cytokine production), HSPCs treated with Dectin-1 ligands produce trained macrophages (higher proinflammatory cytokine production). However, nothing is known about the impact of HSPC exposure to microbes on the function of antigen presenting cells (APCs). In this study we evaluated whether treatment of murine bone marrow HSPCs with a TLR2 or Dectin-1 ligand impacts the antigen presenting capacity of APCs derived from them in vitro. Following activation with microbial ligands or Candida albicans yeasts, APCs derived from TLR2/Dectin-1-programed HSPCs exhibit altered expression of MHCII (signal 1), co-stimulatory molecules (CD40, CD80 and CD86; signal 2) and cytokines (TNF-α, IL-6, IL-12 p40 and IL-2; signal 3). Moreover, APCs derived from TLR2/Dectin-1-programed HSPCs prime enhanced Th1 and Th17 responses, which are important for antifungal defense, in CD4 T cell cocultures. Overall, these results demonstrate for the first time that microbial detection by bone marrow HSPCs can modulate the adaptive immune response by inducing the production of APCs with an altered phenotype. Full article
(This article belongs to the Special Issue Dendritic Cells in Immunity and Inflammation)
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13 pages, 3582 KiB  
Article
TNFα Rescues Dendritic Cell Development in Hematopoietic Stem and Progenitor Cells Lacking C/EBPα
by Subramanian Anirudh, Angelika Rosenberger, Elke Schwarzenberger, Carolin Schaefer, Herbert Strobl, Armin Zebisch, Heinz Sill and Albert Wölfler
Cells 2020, 9(5), 1223; https://doi.org/10.3390/cells9051223 - 15 May 2020
Cited by 3 | Viewed by 2762
Abstract
Dendritic cells (DCs) are crucial effectors of the immune system, which are formed from hematopoietic stem and progenitor cells (HSPCs) by a multistep process regulated by cytokines and distinct transcriptional mechanisms. C/EBPα is an important myeloid transcription factor, but its role in DC [...] Read more.
Dendritic cells (DCs) are crucial effectors of the immune system, which are formed from hematopoietic stem and progenitor cells (HSPCs) by a multistep process regulated by cytokines and distinct transcriptional mechanisms. C/EBPα is an important myeloid transcription factor, but its role in DC formation is not well defined. Using a CebpaCre-EYFP reporter mouse model, we show that the majority of splenic conventional DCs are derived from Cebpa-expressing HSPCs. Furthermore, HSPCs isolated from Cebpa knockout (KO) mice exhibited a marked reduced ability to form mature DCs after in vitro culture with FLT3L. Differentiation analysis revealed that C/EBPα was needed for the formation of monocytic dendritic progenitors and their transition to common dendritic progenitors. Gene expression analysis and cytokine profiling of culture supernatants showed significant downregulation of inflammatory cytokines, including TNFα and IL-1β as well as distinct chemokines in KO HSPCs. In addition, TNFα-induced genes were among the most dysregulated genes in KO HSPCs. Intriguingly, supplementation of in vitro cultures with TNFα at least partially rescued DC formation of KO HSPCs, resulting in fully functional, mature DCs. In conclusion, these results reveal an important role of C/EBPα in early DC development, which in part can be substituted by the inflammatory cytokine TNFα. Full article
(This article belongs to the Special Issue Dendritic Cells in Immunity and Inflammation)
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Review

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22 pages, 1161 KiB  
Review
Cross-Presenting XCR1+ Dendritic Cells as Targets for Cancer Immunotherapy
by Katherine M. Audsley, Alison M. McDonnell and Jason Waithman
Cells 2020, 9(3), 565; https://doi.org/10.3390/cells9030565 - 28 Feb 2020
Cited by 28 | Viewed by 6169
Abstract
The use of dendritic cells (DCs) to generate effective anti-tumor T cell immunity has garnered much attention over the last thirty-plus years. Despite this, limited clinical benefit has been demonstrated thus far. There has been a revival of interest in DC-based treatment strategies [...] Read more.
The use of dendritic cells (DCs) to generate effective anti-tumor T cell immunity has garnered much attention over the last thirty-plus years. Despite this, limited clinical benefit has been demonstrated thus far. There has been a revival of interest in DC-based treatment strategies following the remarkable patient responses observed with novel checkpoint blockade therapies, due to the potential for synergistic treatment. Cross-presenting DCs are recognized for their ability to prime CD8+ T cell responses to directly induce tumor death. Consequently, they are an attractive target for next-generation DC-based strategies. In this review, we define the universal classification system for cross-presenting DCs, and the vital role of this subset in mediating anti-tumor immunity. Furthermore, we will detail methods of targeting these DCs both ex vivo and in vivo to boost their function and drive effective anti-tumor responses. Full article
(This article belongs to the Special Issue Dendritic Cells in Immunity and Inflammation)
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