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| Open AccessMarch1-dependent modulation of donor MHC II on CD103+ dendritic cells mitigates alloimmunity
Donor-derived dendritic cells (do-DC) in the graft can contribute to the induction of alloimmunity and tissue rejection, but how do-DC can be targeted for improving graft survival is unclear. Here the authors show that reducing MHC-II expression on do-DCs by DnaK pre-treatment can decrease the priming of alloimmunity and prolong graft survival in mouse models.
- Thiago J. Borges
- , Naoka Murakami
- & Cristina Bonorino
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| Open AccessSingle-cell analysis reveals that stochasticity and paracrine signaling control interferon-alpha production by plasmacytoid dendritic cells
Plasmacytoid dendritic cells (pDC) are a pivotal component of the immune system. Here, the authors utilize single-cell microfluidics to interrogate the human pDC compartment and reveal a subset of type I IFN secreting pDCs that is regulated by stochastic gene expression and amplified by microenvironmental cues.
- Florian Wimmers
- , Nikita Subedi
- & Jurjen Tel
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| Open AccessMyeloid apolipoprotein E controls dendritic cell antigen presentation and T cell activation
Cholesterol homeostasis can modulate immunity via multiple pathways. Here the authors show that apolipoprotein E, an important regulator of cholesterol, produced by myeloid cells can regulate T cell activation by controlling the antigen presentation activity of dendritic cells in both humans and mice.
- Fabrizia Bonacina
- , David Coe
- & Giuseppe D. Norata
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| Open AccessPriming of dendritic cells by DNA-containing extracellular vesicles from activated T cells through antigen-driven contacts
T cells are activated by antigen-bearing dendritic cells (DC), but how DCs receive reciprocal activating signals from T cells is still unclear. Here the authors show that mitochondrial DNA-containing extracellular vesicles from activated T cells can prime DCs for anti-viral immunity via the cGAS/STING DNA sensing pathways.
- Daniel Torralba
- , Francesc Baixauli
- & Francisco Sánchez-Madrid
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| Open AccessHuman in vivo-generated monocyte-derived dendritic cells and macrophages cross-present antigens through a vacuolar pathway
Cross-presentation, or the presentation of exogenous antigens on MHC-I, is thought to be restricted to dendritic cells (DCs). Here the authors show that human DCs and macrophages developed in vivo from monocytes can both perform cross-presentation using a non-conventional pathway, but only DCs are capable of inducing cytotoxic CD8+ T cells.
- Tsing-Lee Tang-Huau
- , Paul Gueguen
- & Elodie Segura
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| Open AccessGlycolytic metabolism is essential for CCR7 oligomerization and dendritic cell migration
The activation of dendritic cells (DC) is associated with a metabolic switch from oxidative to glycolytic metabolism. Here, the authors show that both strong and weak stimuli cause an immediate increase in glycolysis, but only strong stimuli induce long-term glycolytic reprogramming.
- Hannah Guak
- , Sara Al Habyan
- & Connie. M. Krawczyk
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| Open AccessMitochondrial reactive oxygen species regulate the induction of CD8+ T cells by plasmacytoid dendritic cells
Cross-presentation allows exogenous antigens to be presented by the major histocompatibility I pathway. Here the authors show that the inducible cross-presentation by plasmacytoid dendritic cells is modulated by mitochondria-originated reactive oxygen species.
- Marine Oberkampf
- , Camille Guillerey
- & Gilles Dadaglio
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Article
| Open AccessLymphotoxin α fine-tunes T cell clonal deletion by regulating thymic entry of antigen-presenting cells
Autoreactive T cells are removed during their development in the thymus through the functions of medullary thymic epithelial cells (mTEC) and dendritic cells (DC), a process termed negative selection. Here the authors show that mTEC-T cell crosstalk and lymphotoxin α signalling are essential for the proper recruitment of DCs into the thymus.
- Noëlla Lopes
- , Jonathan Charaix
- & Magali Irla
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| Open AccessIkaros family zinc finger 1 regulates dendritic cell development and function in humans
IKZF1 is a transcription factor known to regulate mammalian B-cell development. Here the authors show that IKZF1 is required for human pDC development and regulation of DC cytokine production in patients with IKZF1 haploinsufficiency, findings which are recapitulated in lenalidomide-induced IKZF1 deficiency.
- Urszula Cytlak
- , Anastasia Resteu
- & Venetia Bigley
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Article
| Open AccessCalcineurin-mediated IL-2 production by CD11chighMHCII+ myeloid cells is crucial for intestinal immune homeostasis
Treg cells can maintain intestinal homeostasis and limit intestinal bowel disease. Here the authors use a mouse model of spontaneous colitis to show that calcineurin-NFAT-induced IL-2 production by dendritic cells regulates the balance between Treg and effector T cells in the gut lamina propria.
- Andrea Mencarelli
- , Hanif Javanmard Khameneh
- & Alessandra Mortellaro
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Article
| Open AccessFcαRI co-stimulation converts human intestinal CD103+ dendritic cells into pro-inflammatory cells through glycolytic reprogramming
Dendritic cells (DC) are important for maintaining immune homeostasis in the gut, but how they promote intestinal inflammation upon bacterial infection is still unclear. Here the authors show that IgA immune complexes induce proinflammatory cytokine production by metabolic reprogramming of otherwise tolerogenic human CD103+ DCs.
- Ivo S. Hansen
- , Lisette Krabbendam
- & Jeroen den Dunnen
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Article
| Open AccessTNF blockade induces a dysregulated type I interferon response without autoimmunity in paradoxical psoriasis
The pathogenesis of paradoxical psoriasis in patients receiving anti-TNF treatments for classical psoriasis is unclear. Here, the authors show that anti-TNF drugs enhance the production of type I interferon by plasmacytoid dendritic cells, causing skin lesions that, unlike classical psoriasis, lack T- cell autoimmunity.
- Curdin Conrad
- , Jeremy Di Domizio
- & Michel Gilliet
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Article
| Open AccessMigratory dendritic cells acquire and present lymphatic endothelial cell-archived antigens during lymph node contraction
Viral infection and vaccination both induce lasting persistence of antigens for protective responses. Here the authors show that migratory dendritic cells, independent of the transcription factor BatF3 for their development, contribute to “archived antigen” exchange with lymphatic endothelial cells.
- Ross M. Kedl
- , Robin S. Lindsay
- & Beth A. Jirón Tamburini
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| Open AccessTLR7 mediated viral recognition results in focal type I interferon secretion by dendritic cells
Antiviral immune responses involve clustering of plasmacytoid dendritic cells (pDC) in response to endosomal TLR7-mediated sensing of viral RNA. Here the authors show the GTPase Arl8b controls translocation of TLR7+ endosomes to the periphery of the cell via microtubule interactions, thus enabling pDC clustering and type I interferon production.
- Shin-Ichiroh Saitoh
- , Fumiko Abe
- & Kensuke Miyake
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| Open AccessBAD-LAMP controls TLR9 trafficking and signalling in human plasmacytoid dendritic cells
TLR9 is highly expressed by plasmacytoid dendritic cells and detects nucleic acids, but to discriminate between host and microbial nucleic acids TLR9 is sorted into different endosomal compartments. Here the authors show that BAD-LAMP limits type 1 interferon responses by sorting TLR9 to late endosomal compartments.
- Alexis Combes
- , Voahirana Camosseto
- & Evelina Gatti
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| Open AccessTGFβR signalling controls CD103+CD11b+ dendritic cell development in the intestine
Developmental cues for the different dendritic cell (DC) subsets in the intestine are yet to be defined. Here the authors show that TGFβR1 signalling is needed for development of CD103+CD11b+ intestinal DCs from CD103−CD11b+ cells and that they contribute to the generation of Th17 and regulatory T cells
- C. C. Bain
- , J. Montgomery
- & A. McI. Mowat
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Article
| Open AccessEnhanced anti-tumour immunity requires the interplay between resident and circulating memory CD8+ T cells
Circulating memory cells include central memory T cells retaining the ability to enter the lymph nodes whereas tissue resident memory cells are confined to the parenchymal tissues. Here the authors explore the interplay between the two T-cell types and show that both cooperate in anti-tumour immunity.
- Michel Enamorado
- , Salvador Iborra
- & David Sancho
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| Open AccessMicroRNA-34a dependent regulation of AXL controls the activation of dendritic cells in inflammatory arthritis
Axl is a TAM receptor that can inhibit Toll-like receptor (TLR) -induced pro-inflammatory production by dendritic cells (DC). Here the authors show that miR-34a targets Axl to control CD1c+ DC activity in mice, and that miR-34a-deficient mice are resistant to collagen-induced arthritis, whereas DCs from patients with rheumatoid arthritis have high levels of miR- 34a.
- Mariola Kurowska-Stolarska
- , Stefano Alivernini
- & Iain B. McInnes
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| Open AccessHSPs drive dichotomous T-cell immune responses via DNA methylome remodelling in antigen presenting cells
Low dose of the heat shock protein gp96 can drive effector T-cell responses, yet high-dose gp96 is immunosuppressive by expanding the regulatory T-cell population. Here the authors explain this dichotomy by showing that high-dose gp96 can drive plasmacytoid dendritic cell expression of neuropilin-1, thus functionally supporting interaction with Treg cells.
- Lauren B. Kinner-Bibeau
- , Abigail L. Sedlacek
- & Robert J. Binder
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Article
| Open AccessGlucose represses dendritic cell-induced T cell responses
Glucose is an important nutrient that feeds into glycolytic control of T cell function and differentiation. Here the authors show that T cells are superior to dendritic cells (DC) at glucose uptake, and by depriving DCs of this nutrient in their microenvironment T cells activate DC proinflammatory functions, which in turn enhance T cell effector functions in DC-T cell cocultures.
- Simon J. Lawless
- , Nidhi Kedia-Mehta
- & David K. Finlay
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| Open AccessSrc family kinases Fyn and Lyn are constitutively activated and mediate plasmacytoid dendritic cell responses
Type I interferon responses are a core immunoregulatory function of plasmacytoid dendritic cells (pDCs). Here the authors show that SFK family members, including Lyn and Fyn, control type I interferon production in human and mouse pDCs.
- S. Dallari
- , M. Macal
- & E. I. Zuniga
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| Open AccessCD40-signalling abrogates induction of RORγt+ Treg cells by intestinal CD103+ DCs and causes fatal colitis
CD103+ dendritic cells induce iTreg cells to maintain immune balance in the gut, but how CD40-signalling regulates this process is unclear. Here the authors show that mice with constitutive CD11c-specific CD40-signalling have altered CD103+dendritic cell migration, reduced iTreg cell induction, and fatal colitis.
- Christian Barthels
- , Ana Ogrinc
- & Thomas Brocker
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Article
| Open AccessNatural amines inhibit activation of human plasmacytoid dendritic cells through CXCR4 engagement
Plasmacytoid dendritic cells produce type I interferons in response to viral sensing. Here the authors show that amines inhibit these plasmacytoid dendritic cell responses through CXCR4 engagement.
- Nikaïa Smith
- , Nicolas Pietrancosta
- & Jean-Philippe Herbeuval
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Article
| Open AccessDendritic cell MST1 inhibits Th17 differentiation
The differentiation of Th17 cells is central to infection and autoimmunity. Here, the authors show that expression of MST1 by dendritic cells limits IL-6 production and thereby controls Th17 differentiation in immunity to fungal infection and experimental autoimmune encephalomyelitis.
- Chunxiao Li
- , Yujing Bi
- & Guangwei Liu
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Article
| Open AccessThe tumour microenvironment harbours ontogenically distinct dendritic cell populations with opposing effects on tumour immunity
Dendritic cells are antigen-presenting cells consisting of distinct subsets originating from different lineages. Here, the authors identify the subsets of dendritic cells populating the tumour tissue in both mice and humans and find they have opposing functions in regulating the anti-tumour immune response.
- Damya Laoui
- , Jiri Keirsse
- & Jo A. Van Ginderachter
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| Open AccessMonocyte-derived inflammatory Langerhans cells and dermal dendritic cells mediate psoriasis-like inflammation
Imiquimod exacerbates IL-23-induced skin inflammation and models psoriasis in mice. Here the authors show that this pathology is not dependent on resident dendritic cells, but on CCR6-induced immigration of monocyte-derived cells.
- Tej Pratap Singh
- , Howard H. Zhang
- & Joshua M. Farber
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| Open AccessGraft-infiltrating host dendritic cells play a key role in organ transplant rejection
Blocking T cell activation in organ transplantation is important to prevent rejection. Here the authors show that unconventional monocyte-derived host dendritic cells enter allogeneic grafts to amplify the T cell response outside lymph nodes.
- Quan Zhuang
- , Quan Liu
- & Adrian E. Morelli
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| Open AccessDeletion of Wiskott–Aldrich syndrome protein triggers Rac2 activity and increased cross-presentation by dendritic cells
Wiskott–Aldrich syndrome (WAS) is a severe X-linked primary immunodeficiency syndrome. Here, the authors show that loss of WAS gene in dendritic cells results in increased activity of Rac2, increase of phagosomal pH, and more efficient cross-presentation.
- Marisa A. P. Baptista
- , Marton Keszei
- & Lisa S. Westerberg
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| Open AccessBlood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells
Factor XII initiates the intrinsic blood coagulation cascade and the kinin system. Here the authors show that Factor XII is elevated in the blood of multiple sclerosis patients, activates dendritic cells via CD87 and cAMP, and its blockade inhibits immunopathology in a mouse model of the disease.
- Kerstin Göbel
- , Susann Pankratz
- & Sven G. Meuth
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| Open AccessClec4A4 is a regulatory receptor for dendritic cells that impairs inflammation and T-cell immunity
Clec4A4 is a C-type lectin receptor highly expressed by CD8α− dendritic cells. Here the authors show that its loss of function results in enhanced T cell responses and exacerbated autoimmunity, implicating Clec4A4 in limiting activation of the CD8α−dendritic cells.
- Tomofumi Uto
- , Tomohiro Fukaya
- & Katsuaki Sato
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Article
| Open AccessPerinuclear Arp2/3-driven actin polymerization enables nuclear deformation to facilitate cell migration through complex environments
Cell migration through micrometric constraints is limited by low deformability of the nucleus. Here the authors show that in dendritic cells a perinuclear actin network nucleated by Arp2/3 increases nuclear deformation and allows the cells to pass through narrow constrictions, likely by rupturing the nuclear lamina.
- Hawa-Racine Thiam
- , Pablo Vargas
- & Matthieu Piel
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| Open AccessIL-21-mediated non-canonical pathway for IL-1β production in conventional dendritic cells
The proinflammatory cytokine interleukin-1ß (IL-1ß) plays an important role in host defence against pathogens. Here the authors report a non-canonical pathway for IL-1 ß production in conventional dendritic cells that is induced by IL-21 via STAT3-dependent mechanism.
- Chi-Keung Wan
- , Peng Li
- & Warren J. Leonard
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Injectable cryogel-based whole-cell cancer vaccines
Immune responses are induced in the organized, cytokine-rich environment of lymph nodes, which can be mimicked by biomaterials. Here the authors show that injectable sponge-like gels decorated with immunostimulatory factors attract dendritic cells and boost antitumour immune responses in mice.
- Sidi A. Bencherif
- , R. Warren Sands
- & David J. Mooney
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Critical role for syndecan-4 in dendritic cell migration during development of allergic airway inflammation
Syndecan-4 is a surface protein implicated in the regulation of cytoskeleton, adhesion and migration. Here the authors show that blocking syndecan-4 prevents dendritic cell migration into the lung and inhibits the development of allergic airway inflammation in mice.
- Tobias Polte
- , Susanne Petzold
- & Marco Averbeck
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| Open AccessCell migration and antigen capture are antagonistic processes coupled by myosin II in dendritic cells
Dendritic cells alternate between fast and slow migratory behaviours, however in the absence of a component of the antigen processing machinery, migration is uniform and fast. Chabaudet al. now show that slow migration results from the relocalisation of myosin II to the cell front where it promotes antigen capture.
- Mélanie Chabaud
- , Mélina L. Heuzé
- & Ana-Maria Lennon-Duménil
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| Open AccessExosome-delivered microRNAs modulate the inflammatory response to endotoxin
Response to inflammatory stimuli such as endotoxin is coordinated at many levels. Here, the authors show that two microRNAs known to regulate inflammatory response inside the cell are secreted by dendritic cells and modulate inflammatory signalling in the neighbouring cells.
- Margaret Alexander
- , Ruozhen Hu
- & Ryan M. O’Connell
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Article
| Open AccessCD11c-mediated deletion of Flip promotes autoreactivity and inflammatory arthritis
Dendritic cells are critical for initiation of immune responses and for induction of tolerance. Here the authors show that deletion of survival factor c-flip in CD11c-expressing cells subset perturbs CD8a+dendritic cell, NK and macrophage pools, and leads to development of autoimmune arthritis.
- Qi-Quan Huang
- , Harris Perlman
- & Richard M. Pope
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Article
| Open AccessId1 suppresses anti-tumour immune responses and promotes tumour progression by impairing myeloid cell maturation
Tumour progression is promoted by the generation of an immunosuppressive macroenvironment. Here, the authors demonstrate that the Inhibitor of Differentiation 1 promotes the switch from dendritic cell differentiation towards myeloid-derived suppressor cell expansion during tumour progression.
- Marianna Papaspyridonos
- , Irina Matei
- & David Lyden
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Article
| Open AccessA dominant role for the methyl-CpG-binding protein Mbd2 in controlling Th2 induction by dendritic cells
How anti-helminth and allergic immune responses are initiated is poorly understood. Here the authors show that to trigger these responses, dendritic cells specifically require methyl-CpG-binding domain-2, a protein promoting repressed chromatin state.
- Peter C. Cook
- , Heather Owen
- & Andrew S. MacDonald
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Article
| Open AccessTonic endocannabinoid-mediated modulation of GABA release is independent of the CB1 content of axon terminals
A simple model for receptor number–function relationships dictates a positive correlation between receptor content and ligand effect. Here, the authors demonstrate that the degree of type-1 cannabinoid receptor (CB1)-modulated GABA release cannot be predicted from CB1content of axon terminals.
- Nora Lenkey
- , Tekla Kirizs
- & Zoltan Nusser
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Dendritic cells induce Th2-mediated airway inflammatory responses to house dust mite via DNA-dependent protein kinase
House dust mites are a common cause of allergic asthma. Here, the authors show that the Th2-mediated inflammatory responses triggered by mites in mouse airways are mediated by the activation of DNA-dependent protein kinase (DNA-PK) in dendritic cells.
- Amarjit Mishra
- , Alexandra L. Brown
- & Jay H. Chung
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| Open AccessUltrasensitive quantification of TAP-dependent antigen compartmentalization in scarce primary immune cell subsets
Antigenic peptides are loaded into major histocompatibility complex class I (MHC I) molecules after entering the ER via the TAP transporter. Here, Fischbach et al. develop a flow cytometry assay to monitor TAP-dependent peptide translocation that is sensitive enough to use on scarce primary cell subsets.
- Hanna Fischbach
- , Marius Döring
- & Robert Tampé
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Imaging regulatory T cell dynamics and CTLA4-mediated suppression of T cell priming
T regulatory cells (Tregs) prevent immunopathology by inhibiting excessive T-cell activation. Here the authors show interactions between dendritic cells, Tregs and antigen-specific T cells in the lymph node during initiation of the immune response in real time by two-photon microscopy.
- Melanie P. Matheu
- , Shivashankar Othy
- & Michael D. Cahalan
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DNase II-dependent DNA digestion is required for DNA sensing by TLR9
Discrimination between self and microbial DNA by innate receptors such as TLR9 relies on intracellular compartmentalization to increase specificity. Chan et al. show that activation of TLR9 by DNA ligands requires their processing by endolysosomal DNase II, restricting TLR9 activation to this organelle.
- Mei Po Chan
- , Masahiro Onji
- & Kensuke Miyake
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Loss of beta2-integrin-mediated cytoskeletal linkage reprogrammes dendritic cells to a mature migratory phenotype
The molecular mechanisms underlying the effects of beta2-integrins on signalling in immune cells are unclear. Here the authors show that disruption of the interaction between beta2-integrins and kindlin-3 results in increased GM-CSF receptor signalling, affecting dendritic cell activation and migration and Th1 immunity.
- Vicky Louise Morrison
- , Martyn John James
- & Susanna Carola Fagerholm
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| Open AccessLAMTOR2 regulates dendritic cell homeostasis through FLT3-dependent mTOR signalling
LAMTOR2 is involved in mTOR and ERK signalling and plays a role in immunity, but its function in dendritic cells (DCs) is not clear. Here the authors show that deletion of LAMTOR2 in DCs results in increased mTOR signalling, accumulation of Flt3 on the cell surface and excessive DC proliferation in ageing mice.
- Julia M. Scheffler
- , Florian Sparber
- & Lukas A. Huber
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Fucose-based PAMPs prime dendritic cells for follicular T helper cell polarization via DC-SIGN-dependent IL-27 production
Dendritic cells (DCs) initiate distinct arms of immunity in response to different classes of pathogens. Here Gringhuis et al. show that DCs produce IL-27 upon sensing fucose-containing pathogen ligands via DC-SIGN, promoting follicular T helper cell differentiation and antibody production.
- Sonja I. Gringhuis
- , Tanja M. Kaptein
- & Teunis B. H. Geijtenbeek
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Dendritic cell-mediated survival signals in Eμ-Myc B-cell lymphoma depend on the transcription factor C/EBPβ
Dendritic cells (DC) are known to promote cancer progression by suppressing antitumor immunity. Here, Rehm et al. describe a mechanism whereby lymphoma cells induce C/EBPβ activation in DCs, which in turn secrete cytokines that support the proliferation and survival of lymphoma cells.
- Armin Rehm
- , Marcel Gätjen
- & Uta E. Höpken
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Dendritic cell subsets require cis-activation for cytotoxic CD8 T-cell induction
Differentiation into cytotoxic lymphocytes requires T-cell instruction by appropriately activated dendritic cells (DCs). Here the authors show that two DC lineages in the lung are selectively activated by either Toll-like receptor 3 or 7 to induce cytotoxic T-cell function.
- A Nicole Desch
- , Sophie L. Gibbings
- & Claudia Jakubzick