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Article ; Online: Transcriptional regulation of DC fate specification.

Bosteels, Cédric / Scott, Charlotte L

2020 Volume 121, Page(s) 38–46

Abstract: Dendritic cells function in the immune system to instruct adaptive immune cells to respond accordingly to different threats. While conventional dendritic cells can be subdivided into two main subtypes, termed cDC1s and cDC2s, it is clear that further ... ...

Abstract	Dendritic cells function in the immune system to instruct adaptive immune cells to respond accordingly to different threats. While conventional dendritic cells can be subdivided into two main subtypes, termed cDC1s and cDC2s, it is clear that further heterogeneity exists within these subtypes, particularly for cDC2s. Understanding the signals involved in specifying each of these lineages and subtypes thereof is crucial to (i) enable us to determine their specific functions and (ii) put us in a position to be able to target these cells to promote or prevent a specific function in any given disease setting. Although we still have much to learn regarding the specification of these cells, here we review the most recent advances in our understanding of this and highlight some of the next questions for the future.
MeSH term(s)	Animals ; Cell Differentiation/genetics ; Cell Differentiation/immunology ; Cell Lineage/genetics ; Cell Lineage/immunology ; Dendritic Cells/physiology ; Humans ; Transcription Factors/metabolism ; Transcriptional Activation/immunology
Chemical Substances	Transcription Factors
Language	English
Publishing date	2020-03-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	424427-8
ISSN	1872-9142 ; 0161-5890
ISSN (online)	1872-9142
ISSN	0161-5890
DOI	10.1016/j.molimm.2020.02.021
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Article: Transcriptional regulation of DC fate specification

Bosteels, Cédric / Scott, Charlotte L

Molecular immunology. 2020 May, v. 121

2020

Abstract	Dendritic cells function in the immune system to instruct adaptive immune cells to respond accordingly to different threats. While conventional dendritic cells can be subdivided into two main subtypes, termed cDC1s and cDC2s, it is clear that further heterogeneity exists within these subtypes, particularly for cDC2s. Understanding the signals involved in specifying each of these lineages and subtypes thereof is crucial to (i) enable us to determine their specific functions and (ii) put us in a position to be able to target these cells to promote or prevent a specific function in any given disease setting. Although we still have much to learn regarding the specification of these cells, here we review the most recent advances in our understanding of this and highlight some of the next questions for the future.
Keywords	dendritic cells ; macrophages ; transcription (genetics)
Language	English
Dates of publication	2020-05
Size	p. 38-46.
Publishing place	Elsevier Ltd
Document type	Article
ZDB-ID	424427-8
ISSN	1872-9142 ; 0161-5890
ISSN (online)	1872-9142
ISSN	0161-5890
DOI	10.1016/j.molimm.2020.02.021
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Article ; Online: Isolation of Conventional Murine Lung Dendritic Cell Subsets.

De Leeuw, Elisabeth / Bosteels, Cédric / Lambrecht, Bart N / Hammad, Hamida

Methods in molecular biology (Clifton, N.J.)

2022 Volume 2506, Page(s) 237–255

Abstract: In the lungs, immune cells make contact with different antigens every day. This requires an adequate immune response. Dendritic cells (DCs) form a dense network in the respiratory mucosa and continuously sample inhaled allergens. They play an important ... ...

Abstract	In the lungs, immune cells make contact with different antigens every day. This requires an adequate immune response. Dendritic cells (DCs) form a dense network in the respiratory mucosa and continuously sample inhaled allergens. They play an important role in bridging innate and adaptive immunity. DCs are classically divided into plasmacytoid DCs (pDCs) and conventional DCs (cDCs). cDCs in the steady-state are further subdivided into cDC1s and cDC2s based on their ontogeny and distinct non-redundant functions. Recently, a hyperactivated state of cDC2s has been described that arises during inflammation, coined inflammatory cDC2s (inf-cDC2s) that phenotypically mimics monocyte-derived cells and has a hybrid cDC1/macrophage functional identity. This chapter describes different enrichment methods and a fluorescence-activated cell sorting protocol that in combination allow for discrimination and isolation of pure DC subsets from the murine lung. The chapter represents an up-to-date, universal framework that can be adapted to other tissues and species which is an added value in intra- and interspecies comparative research.
MeSH term(s)	Adaptive Immunity ; Allergens ; Animals ; Dendritic Cells ; Flow Cytometry/methods ; Lung ; Mice
Chemical Substances	Allergens
Language	English
Publishing date	2022-06-30
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-2364-0_17
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Article ; Online: Isolation of Conventional Murine Lung Dendritic Cell Subsets.

Bosteels, Cédric / Lambrecht, Bart N / Hammad, Hamida

Current protocols in immunology

2018 Volume 120, Page(s) 3.7B.1–3.7B.16

Abstract: The lungs are continuously exposed to environmental threats, requiring an adequate and stringent immune response of a heterogeneous set of effector cells. Dendritic cells (DCs) form a dense network in the respiratory mucosa and act as the central ... ...

Abstract	The lungs are continuously exposed to environmental threats, requiring an adequate and stringent immune response of a heterogeneous set of effector cells. Dendritic cells (DCs) form a dense network in the respiratory mucosa and act as the central regulators of the different components of this response, both sensing the nature of the threats and precisely coordinating the effector mechanisms best suited for overcoming it. The DCs are classically subdivided in two main groups, plasmacytoid DCs (pDCs) and conventional DCs (cDCs), the latter being further subdivided into cDC1s and cDC2s based on ontogeny and their distinct non-redundant functions. This protocol provides different enrichment methods and represents an up-to-date, universal framework that uses a minimal set of highly specific lineage markers to discriminate and sort pure cDC subsets from the murine lung but also across tissues and species which is an added value in intra- and interspecies comparative research. © 2018 by John Wiley & Sons, Inc.
MeSH term(s)	Animals ; CD11c Antigen ; Cell Separation ; Dendritic Cells/cytology ; Lung/cytology ; Mice ; Staining and Labeling
Chemical Substances	CD11c Antigen
Language	English
Publishing date	2018-02-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1934-368X
ISSN (online)	1934-368X
DOI	10.1002/cpim.39
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Article ; Online: LXR signaling controls homeostatic dendritic cell maturation.

Bosteels, Victor / Maréchal, Sandra / De Nolf, Clint / Rennen, Sofie / Maelfait, Jonathan / Tavernier, Simon J / Vetters, Jessica / Van De Velde, Evelien / Fayazpour, Farzaneh / Deswarte, Kim / Lamoot, Alexander / Van Duyse, Julie / Martens, Liesbet / Bosteels, Cédric / Roelandt, Ria / Emmaneel, Annelies / Van Gassen, Sofie / Boon, Louis / Van Isterdael, Gert /

Guillas, Isabelle / Vandamme, Niels / Höglinger, Doris / De Geest, Bruno G / Le Goff, Wilfried / Saeys, Yvan / Ravichandran, Kodi S / Lambrecht, Bart N / Janssens, Sophie

Science immunology

2023 Volume 8, Issue 83, Page(s) eadd3955

Abstract: Dendritic cells (DCs) mature in an immunogenic or tolerogenic manner depending on the context in which an antigen is perceived, preserving the balance between immunity and tolerance. Whereas the pathways driving immunogenic maturation in response to ... ...

Abstract	Dendritic cells (DCs) mature in an immunogenic or tolerogenic manner depending on the context in which an antigen is perceived, preserving the balance between immunity and tolerance. Whereas the pathways driving immunogenic maturation in response to infectious insults are well-characterized, the signals that drive tolerogenic maturation during homeostasis are still poorly understood. We found that the engulfment of apoptotic cells triggered homeostatic maturation of type 1 conventional DCs (cDC1s) within the spleen. This maturation process could be mimicked by engulfment of empty, nonadjuvanted lipid nanoparticles (LNPs), was marked by intracellular accumulation of cholesterol, and was highly specific to cDC1s. Engulfment of either apoptotic cells or cholesterol-rich LNPs led to the activation of the liver X receptor (LXR) pathway, which promotes the efflux of cellular cholesterol, and repressed genes associated with immunogenic maturation. In contrast, simultaneous engagement of TLR3 to mimic viral infection via administration of poly(I:C)-adjuvanted LNPs repressed the LXR pathway, thus delaying cellular cholesterol efflux and inducing genes that promote T cell-mediated immunity. These data demonstrate that conserved cellular cholesterol efflux pathways are differentially regulated in tolerogenic versus immunogenic cDC1s and suggest that administration of nonadjuvanted cholesterol-rich LNPs may be an approach for inducing tolerogenic DC maturation.
MeSH term(s)	Liver X Receptors/metabolism ; Signal Transduction/genetics ; Homeostasis ; Dendritic Cells ; Cholesterol
Chemical Substances	Liver X Receptors ; Cholesterol (97C5T2UQ7J)
Language	English
Publishing date	2023-05-12
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.add3955
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Article ; Online: A complement atlas identifies interleukin-6-dependent alternative pathway dysregulation as a key druggable feature of COVID-19.

Van Damme, Karel F A / Hoste, Levi / Declercq, Jozefien / De Leeuw, Elisabeth / Maes, Bastiaan / Martens, Liesbet / Colman, Roos / Browaeys, Robin / Bosteels, Cédric / Verwaerde, Stijn / Vermeulen, Nicky / Lameire, Sahine / Debeuf, Nincy / Deckers, Julie / Stordeur, Patrick / Depuydt, Pieter / Van Braeckel, Eva / Vandekerckhove, Linos / Guilliams, Martin /

Schetters, Sjoerd T T / Haerynck, Filomeen / Tavernier, Simon J / Lambrecht, Bart N

Science translational medicine

2023 Volume 15, Issue 710, Page(s) eadi0252

Abstract: Improvements in COVID-19 treatments, especially for the critically ill, require deeper understanding of the mechanisms driving disease pathology. The complement system is not only a crucial component of innate host defense but can also contribute to ... ...

Abstract	Improvements in COVID-19 treatments, especially for the critically ill, require deeper understanding of the mechanisms driving disease pathology. The complement system is not only a crucial component of innate host defense but can also contribute to tissue injury. Although all complement pathways have been implicated in COVID-19 pathogenesis, the upstream drivers and downstream effects on tissue injury remain poorly defined. We demonstrate that complement activation is primarily mediated by the alternative pathway, and we provide a comprehensive atlas of the complement alterations around the time of respiratory deterioration. Proteomic and single-cell sequencing mapping across cell types and tissues reveals a division of labor between lung epithelial, stromal, and myeloid cells in complement production, in addition to liver-derived factors. We identify IL-6 and STAT1/3 signaling as an upstream driver of complement responses, linking complement dysregulation to approved COVID-19 therapies. Furthermore, an exploratory proteomic study indicates that inhibition of complement C5 decreases epithelial damage and markers of disease severity. Collectively, these results support complement dysregulation as a key druggable feature of COVID-19.
MeSH term(s)	Humans ; Interleukin-6 ; Proteomics ; COVID-19 ; Complement System Proteins ; Complement Activation
Chemical Substances	Interleukin-6 ; Complement System Proteins (9007-36-7)
Language	English
Publishing date	2023-08-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.adi0252
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Article ; Online: CCR2- and Flt3-Dependent Inflammatory Conventional Type 2 Dendritic Cells Are Necessary for the Induction of Adaptive Immunity by the Human Vaccine Adjuvant System AS01.

Bosteels, Cedric / Fierens, Kaat / De Prijck, Sofie / Van Moorleghem, Justine / Vanheerswynghels, Manon / De Wolf, Caroline / Chalon, Aurélie / Collignon, Catherine / Hammad, Hamida / Didierlaurent, Arnaud M / Lambrecht, Bart N

Frontiers in immunology

2021 Volume 11, Page(s) 606805

Abstract: The Adjuvant System AS01 contains monophosphoryl lipid A (MPL) and the saponin QS-21 in a liposomal formulation. AS01 is included in recently developed vaccines against malaria and varicella zoster virus. Like for many other adjuvants, induction of ... ...

Abstract	The Adjuvant System AS01 contains monophosphoryl lipid A (MPL) and the saponin QS-21 in a liposomal formulation. AS01 is included in recently developed vaccines against malaria and varicella zoster virus. Like for many other adjuvants, induction of adaptive immunity by AS01 is highly dependent on the ability to recruit and activate dendritic cells (DCs) that migrate to the draining lymph node for T and B cell stimulation. The objective of this study was to more precisely address the contribution of the different conventional (cDC) and monocyte-derived DC (MC) subsets in the orchestration of the adaptive immune response after immunization with AS01 adjuvanted vaccine. The combination of MPL and QS-21 in AS01 induced strong recruitment of CD26
MeSH term(s)	Adaptive Immunity/drug effects ; Adjuvants, Immunologic/pharmacology ; Animals ; CD4-Positive T-Lymphocytes/drug effects ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/drug effects ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/metabolism ; Cells, Cultured ; Coculture Techniques ; Dendritic Cells/drug effects ; Dendritic Cells/immunology ; Dendritic Cells/metabolism ; Female ; Herpes Zoster Vaccine/pharmacology ; Immunization ; Lipid A/analogs & derivatives ; Lipid A/pharmacology ; Liposomes ; Mice, Inbred C57BL ; Mice, Knockout ; Ovalbumin/pharmacology ; Receptors, CCR2/genetics ; Receptors, CCR2/metabolism ; Saponins/pharmacology ; Signal Transduction ; Viral Envelope Proteins/pharmacology ; fms-Like Tyrosine Kinase 3/genetics ; fms-Like Tyrosine Kinase 3/metabolism ; Mice
Chemical Substances	Adjuvants, Immunologic ; Ccr2 protein, mouse ; Herpes Zoster Vaccine ; Lipid A ; Liposomes ; Receptors, CCR2 ; Saponins ; Viral Envelope Proteins ; glycoprotein E, varicella-zoster virus ; saponin QA-21V1 (61H83WZX3U) ; Ovalbumin (9006-59-1) ; Flt3 protein, mouse (EC 2.7.10.1) ; fms-Like Tyrosine Kinase 3 (EC 2.7.10.1) ; monophosphoryl lipid A (MWC0ET1L2P)
Language	English
Publishing date	2021-01-14
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2020.606805
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Article: Twelve-year follow-up study after endoscopic sinus surgery in patients with chronic rhinosinusitis with nasal polyposis.

Calus, Lien / Van Bruaene, Nicholas / Bosteels, Cedric / Dejonckheere, Sarah / Van Zele, Thibaut / Holtappels, Gabrielle / Bachert, Claus / Gevaert, Philippe

Clinical and translational allergy

2019 Volume 9, Page(s) 30

Abstract: Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a therapeutic challenge because of the high recurrence rate. Surgical intervention should be considered in patients who fail to improve after medical treatment. We monitored recurrence ... ...

Abstract	Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is a therapeutic challenge because of the high recurrence rate. Surgical intervention should be considered in patients who fail to improve after medical treatment. We monitored recurrence and revision surgery over 12 years after endoscopic sinus surgery in CRSwNP patients. Methods: In this prospective cohort study, 47 patients with CRSwNP, who underwent primary or revision extended endoscopic sinus surgery, were followed. Clinical symptoms and total nasal endoscopic polyp score were evaluated before, 6 years and 12 years after surgery. Results: Twelve years after surgery, 38 out of 47 patients (80.9%) were available for examination. There still was a significantly better symptom score and total nasal endoscopic polyp score compared to before surgery (P < 0.001). Within the 12-year follow-up period, 30 out of 38 patients developed recurrent nasal polyps, of which 14 patients underwent additional revision surgery. Comorbid allergic sensitization and tissue IL-5 levels were found to be significant predictors for the need of revision surgery. Conclusions: This long-term cohort study, investigating the outcome after surgery in CRSwNP, showed that, despite the low number of patients, 78.9% of patients with CRSwNP were subject to recurrence of the disease and 36.8% to revision surgery over a 12-year period.
Language	English
Publishing date	2019-06-14
Publishing country	England
Document type	Journal Article
ZDB-ID	2630865-4
ISSN	2045-7022
ISSN	2045-7022
DOI	10.1186/s13601-019-0269-4
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Article ; Online: Loss of GM-CSF-dependent instruction of alveolar macrophages in COVID-19 provides a rationale for inhaled GM-CSF treatment.

Bosteels, Cedric / Van Damme, Karel F A / De Leeuw, Elisabeth / Declercq, Jozefien / Maes, Bastiaan / Bosteels, Victor / Hoste, Levi / Naesens, Leslie / Debeuf, Nincy / Deckers, Julie / Cole, Basiel / Pardons, Marion / Weiskopf, Daniela / Sette, Alessandro / Weygaerde, Yannick Vande / Malfait, Thomas / Vandecasteele, Stefaan J / Demedts, Ingel K / Slabbynck, Hans /

Allard, Sabine / Depuydt, Pieter / Van Braeckel, Eva / De Clercq, Jozefien / Martens, Liesbet / Dupont, Sam / Seurinck, Ruth / Vandamme, Niels / Haerynck, Filomeen / Roychowdhury, Debasish F / Vandekerckhove, Linos / Guilliams, Martin / Tavernier, Simon J / Lambrecht, Bart N

Cell reports. Medicine

2022 , Page(s) 100833

Abstract: GM-CSF promotes myelopoiesis and inflammation, and GM-CSF blockade is being evaluated as a treatment for COVID-19-associated hyperinflammation. Alveolar GM-CSF is, however, required for monocytes to differentiate into alveolar macrophages (AMs) that ... ...

Abstract	GM-CSF promotes myelopoiesis and inflammation, and GM-CSF blockade is being evaluated as a treatment for COVID-19-associated hyperinflammation. Alveolar GM-CSF is, however, required for monocytes to differentiate into alveolar macrophages (AMs) that control alveolar homeostasis. By mapping cross-species AM development to clinical lung samples, we discovered that COVID-19 is marked by defective GM-CSF-dependent AM instruction and accumulation of pro-inflammatory macrophages. In a multi-center, open-label RCT in 81 non-ventilated COVID-19 patients with respiratory failure, we found that inhalation of rhu-GM-CSF did not improve mean oxygenation parameters compared with standard treatment. However, more patients on GM-CSF had a clinical response, and GM-CSF inhalation induced higher numbers of virus-specific CD8 effector lymphocytes and class-switched B cells, without exacerbating systemic hyperinflammation. This translational proof-of-concept study provides a rationale for further testing of inhaled GM-CSF as a non-invasive treatment to improve alveolar gas exchange and simultaneously boost antiviral immunity in COVID-19. This study is registered at ClinicalTrials.gov (NCT04326920) and EudraCT (2020-001254-22).
Language	English
Publishing date	2022-11-15
Publishing country	United States
Document type	Journal Article
ISSN	2666-3791
ISSN (online)	2666-3791
DOI	10.1016/j.xcrm.2022.100833
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Article ; Online: Correction to: Treatment of severely ill COVID-19 patients with anti-interleukin drugs (COV-AID): A structured summary of a study protocol for a randomised controlled trial.

Maes, Bastiaan / Bosteels, Cedric / De Leeuw, Elisabeth / Declercq, Jozefien / Van Damme, Karel / Delporte, Anja / Demeyere, Bénédicte / Vermeersch, Stéfanie / Vuylsteke, Marnik / Willaert, Joren / Bollé, Laura / Vanbiervliet, Yuri / Decuypere, Jana / Libeer, Frederick / Vandecasteele, Stefaan / Peene, Isabelle / Lambrecht, Bart N

Trials

2020 Volume 21, Issue 1, Page(s) 556

Abstract: An amendment to this paper has been published and can be accessed via the original article. ...

Abstract	An amendment to this paper has been published and can be accessed via the original article.
Keywords	covid19
Language	English
Publishing date	2020-06-22
Publishing country	England
Document type	Journal Article ; Published Erratum
ZDB-ID	2040523-6
ISSN	1745-6215 ; 1468-6694 ; 1745-6215
ISSN (online)	1745-6215
ISSN	1468-6694 ; 1745-6215
DOI	10.1186/s13063-020-04519-4
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