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Article ; Online: Monocyte TREM-1 Levels Associate With Anti-TNF Responsiveness in IBD Through Autophagy and Fcγ-Receptor Signaling Pathways.

Prins, Marileen M / Verstockt, Bram / Ferrante, Marc / Vermeire, Séverine / Wildenberg, Manon E / Koelink, Pim J

2021 Volume 12, Page(s) 627535

Abstract: The expression ... ...

Abstract	The expression of
Language	English
Publishing date	2021-03-15
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.2021.627535
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Additional Stability Testing of Cryopreserved Intestinal Biopsies for Downstream Flow Cytometric Analysis.

Vande Casteele, Niels / Wildenberg, Manon E

Journal of immunological methods

2018 Volume 474, Page(s) 112517

MeSH term(s)	Biopsy ; Cryopreservation/methods ; Flow Cytometry ; Humans ; Intestines ; Specimen Handling/methods
Language	English
Publishing date	2018-09-08
Publishing country	Netherlands
Document type	Letter
ZDB-ID	120142-6
ISSN	1872-7905 ; 0022-1759
ISSN (online)	1872-7905
ISSN	0022-1759
DOI	10.1016/j.jim.2018.09.005
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Zs.A 795: Show issues

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Article: Role of the Mesentery in Crohn's Terminal Ileitis.

Becker, Marte A J / Does de Willebois, Eline M L van der / Bemelman, Willem A / Wildenberg, Manon E / Buskens, Christianne J

Clinics in colon and rectal surgery

2022 Volume 35, Issue 4, Page(s) 316–320

Abstract: Despite the longstanding awareness of the presence of mesenteric alterations in Crohn's disease, the functional and clinical consequences of these alterations remain a topic of debate. Guidelines advise a limited resection without resection of the ... ...

Abstract	Despite the longstanding awareness of the presence of mesenteric alterations in Crohn's disease, the functional and clinical consequences of these alterations remain a topic of debate. Guidelines advise a limited resection without resection of the adjacent mesentery to prevent short bowel syndrome and postoperative complications. However, recently mesenteric resection has been proposed as an alternative to reduce recurrence rates in Crohn's disease patients. Here, we evaluate the data available on this topic in terminal ileitis, both from a fundamental research point of view and clinical perspective.
Language	English
Publishing date	2022-07-04
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2048635-2
ISSN	1531-0043
ISSN	1531-0043
DOI	10.1055/s-0042-1743589
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Zs.A 3931: Show issues

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Article ; Online: Berbamine suppresses intestinal SARS-CoV-2 infection via a BNIP3-dependent autophagy blockade.

Cloherty, Alexandra P M / Rader, Anusca G / Patel, Kharishma S / Pérez-Vargas, Jimena / Thompson, Connor A H / Ennis, Siobhan / Niikura, Masahiro / Wildenberg, Manon E / Muncan, Vanesa / Schreurs, Renée R C E / Jean, François / Ribeiro, Carla M S

Emerging microbes & infections

2023 Volume 12, Issue 1, Page(s) 2195020

Abstract: SARS-CoV-2, the causative virus of COVID-19, continues to threaten global public health. COVID-19 is a multi-organ disease, causing not only respiratory distress, but also extrapulmonary manifestations, including gastrointestinal symptoms with SARS-CoV-2 ...

Abstract	SARS-CoV-2, the causative virus of COVID-19, continues to threaten global public health. COVID-19 is a multi-organ disease, causing not only respiratory distress, but also extrapulmonary manifestations, including gastrointestinal symptoms with SARS-CoV-2 RNA shedding in stool long after respiratory clearance. Despite global vaccination and existing antiviral treatments, variants of concern are still emerging and circulating. Of note, new Omicron BA.5 sublineages both increasingly evade neutralizing antibodies and demonstrate an increased preference for entry via the endocytic entry route. Alternative to direct-acting antivirals, host-directed therapies interfere with host mechanisms hijacked by viruses, and enhance cell-mediated resistance with a reduced likelihood of drug resistance development. Here, we demonstrate that the autophagy-blocking therapeutic berbamine dihydrochloride robustly prevents SARS-CoV-2 acquisition by human intestinal epithelial cells via an autophagy-mediated BNIP3 mechanism. Strikingly, berbamine dihydrochloride exhibited pan-antiviral activity against Omicron subvariants BA.2 and BA.5 at nanomolar potency, providing a proof of concept for the potential for targeting autophagy machinery to thwart infection of current circulating SARS-CoV-2 subvariants. Furthermore, we show that autophagy-blocking therapies limited virus-induced damage to intestinal barrier function, affirming the therapeutic relevance of autophagy manipulation to avert the intestinal permeability associated with acute COVID-19 and post-COVID-19 syndrome. Our findings underscore that SARS-CoV-2 exploits host autophagy machinery for intestinal dissemination and indicate that repurposed autophagy-based antivirals represent a pertinent therapeutic option to boost protection and ameliorate disease pathogenesis against current and future SARS-CoV-2 variants of concern.
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; Antiviral Agents/pharmacology ; Post-Acute COVID-19 Syndrome ; RNA, Viral ; Hepatitis C, Chronic ; Antibodies, Neutralizing ; Autophagy ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus ; Membrane Proteins
Chemical Substances	berbamine (V5KM4XJ0WM) ; Antiviral Agents ; RNA, Viral ; Antibodies, Neutralizing ; Antibodies, Viral ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; BNIP3 protein, human ; Membrane Proteins
Language	English
Publishing date	2023-03-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2681359-2
ISSN	2222-1751 ; 2222-1751
ISSN (online)	2222-1751
ISSN	2222-1751
DOI	10.1080/22221751.2023.2195020
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Article: Recapitulating suckling-to-weaning transition in vitro using fetal intestinal organoids

Garcia, Tânia Martins / Muncan, Vanesa / Navis, Marit / van Elburg, Ruurd M / Wildenberg, Manon E

Journal of visualized experiments. 2019 Nov. 15, , no. 153

2019

Abstract: At the end of the suckling period, many mammalian species undergo major changes in the intestinal epithelium that are associated with the capability to digest solid food. This process is termed suckling-to-weaning transition and results in the ... ...

Abstract	At the end of the suckling period, many mammalian species undergo major changes in the intestinal epithelium that are associated with the capability to digest solid food. This process is termed suckling-to-weaning transition and results in the replacement of neonatal epithelium with adult epithelium which goes hand in hand with metabolic and morphological adjustments. These complex developmental changes are the result of a genetic program that is intrinsic to the intestinal epithelial cells but can, to some extent, be modulated by extrinsic factors. Prolonged culture of mouse primary intestinal epithelial cells from late fetal period, recapitulates suckling-to-weaning transition in vitro. Here, we describe a detailed protocol for mouse fetal intestinal organoid culture best suited to model this process in vitro. We describe several useful assays designed to monitor the change of intestinal functions associated with suckling-to-weaning transition over time. Additionally, we include an example of an extrinsic factor that is capable to affect suckling-to-weaning transition in vivo, as a representation of modulating the timing of suckling-to-weaning transition in vitro. This in vitro approach can be used to study molecular mechanisms of the suckling-to-weaning transition as well as modulators of this process. Importantly, with respect to animal ethics in research, replacing in vivo models by this in vitro model contributes to refinement of animal experiments and possibly to a reduction in the use of animals to study gut maturation processes.
Keywords	adults ; animal ethics ; animal experimentation ; animal use reduction ; animal use refinement ; animal use replacement ; intestinal mucosa ; mice ; suckling
Language	English
Dates of publication	2019-1115
Size	p. e60470.
Publishing place	Journal of Visualized Experiments
Document type	Article
ZDB-ID	2259946-0
ISSN	1940-087X
ISSN	1940-087X
DOI	10.3791/60470
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Thiopurines correct the effects of autophagy impairment on intestinal healing - a potential role for ARHGAP18/RhoA.

Prins, Marileen M C / Giugliano, Francesca P / van Roest, Manon / van de Graaf, Stan F J / Koelink, Pim J / Wildenberg, Manon E

Disease models & mechanisms

2021 Volume 14, Issue 4

Abstract: The ATG16L1 T300A single-nucleotide polymorphism (SNP) is associated with Crohn's disease and causes an autophagy impairment. We have previously shown that this SNP is involved in the migration and hyperactivation of Rac1 in dendritic cells. Mucosal ... ...

Abstract	The ATG16L1 T300A single-nucleotide polymorphism (SNP) is associated with Crohn's disease and causes an autophagy impairment. We have previously shown that this SNP is involved in the migration and hyperactivation of Rac1 in dendritic cells. Mucosal healing, currently the main target for inflammatory bowel disease treatment, depends on restoration of the epithelial barrier and requires appropriate migration of epithelial cells towards and over mucosal lesions. Therefore, we here further investigated the impact of autophagy on epithelial migration. ATG16L1 knockdown was established in the HT29 human colonic epithelial cell line using lentiviral transduction. Migratory capacity was evaluated using scratch assays and RhoAGTP was measured using G-LISA. Immunofluorescent ARHGAP18 and sequestome 1 (SQSTM1; also known as p62) staining was performed on HT29 cells and primary colonic tissue of Crohn's disease patients. We observed that ATG16L1 knockdown cells exhibited decreased autophagy and decreased migration capacity. Furthermore, activity of RhoA was decreased. These characteristics were phenocopied using ATG5 knockdown and pharmacological inhibition of autophagy. The migration defect was dependent on accumulation of SQSTM1 and was alleviated upon SQSTM1 knockdown. Strikingly, thiopurines also mitigated the effects of impaired autophagy. RhoA dysregulation appeared mediated through accumulation of the upstream regulator ARHGAP18, which was observed in cell lines, human foetal organoids and primary colonic tissue. Our results indicate that the ATG16L1 T300A Crohn's disease-associated SNP causes a decrease in migration capacity in epithelial cells, mediated by an increase in SQSTM1 and ARHGAP18 protein and subsequent reduced RhoA activation.
MeSH term(s)	Autophagy/drug effects ; Cell Movement/drug effects ; Epithelial Cells/drug effects ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; GTPase-Activating Proteins/metabolism ; HT29 Cells ; Humans ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/pathology ; Intestines/drug effects ; Intestines/pathology ; Organoids/drug effects ; Organoids/metabolism ; Phenotype ; Sequestosome-1 Protein/metabolism ; Sulfhydryl Compounds/pharmacology ; Wound Healing/drug effects ; rhoA GTP-Binding Protein/metabolism
Chemical Substances	ARHGAP18 protein, human ; GTPase-Activating Proteins ; SQSTM1 protein, human ; Sequestosome-1 Protein ; Sulfhydryl Compounds ; rhoA GTP-Binding Protein (EC 3.6.5.2)
Language	English
Publishing date	2021-04-23
Publishing country	England
Document type	Journal Article
ZDB-ID	2451104-3
ISSN	1754-8411 ; 1754-8403
ISSN (online)	1754-8411
ISSN	1754-8403
DOI	10.1242/dmm.047233
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Article ; Online: High prevalence of ulcerative appendicitis in patients with ulcerative colitis.

Heuthorst, Lianne / Mookhoek, Aart / Wildenberg, Manon E / D'Haens, Geert R / Bemelman, Willem A / Buskens, Christianne J

United European gastroenterology journal

2021 Volume 9, Issue 10, Page(s) 1148–1156

Abstract: Background: Previous studies have indicated that the appendix may be a priming site of ulcerative colitis (UC). Appendectomy is inversely associated with the development of UC, and is suggested to have a beneficial effect on the disease course in ... ...

Abstract	Background: Previous studies have indicated that the appendix may be a priming site of ulcerative colitis (UC). Appendectomy is inversely associated with the development of UC, and is suggested to have a beneficial effect on the disease course in patients with refractory disease. Objective: The aim of the current study was to assess histological features of appendices from patients with UC and their clinical relevance. Methods: Patients with UC in remission and active UC (therapy refractory) that underwent appendectomy between 2012 and 2019 were included. Histological features of UC appendices were compared to those of patients with acute appendicitis and colon carcinoma. The Robarts Histopathology Index (RHI) was used to assess appendiceal inflammation. In patients with active UC, histological and clinical characteristics were compared between patients with and without endoscopic response following appendectomy. Results: In total, 140 appendix specimens were assessed (n = 35 UC remission, n = 35 active UC, n = 35 acute appendicitis, n = 35 colon carcinoma). Histological features of appendices from UC patients looked like UC rather than acute appendicitis. The presence of active appendiceal inflammation was comparable between patients in remission versus active disease (53.7% vs. 46.3%, p = 0.45) and limited versus extensive disease (58.5% vs. 41.5%, p = 0.50). Endoscopic response (Mayo 0-1) following appendectomy, assessed in 28 therapy refractory patients, was more frequently seen in patients with higher RHI scores (RHI > 6: 81.8% vs. RHI ≤ 6: 9.1%, p = 0.03) and limited disease (proctitis/left sided 63.6% vs. pancolitis 36.4%, p = 0.02). Conclusion: The presence of active appendiceal inflammation is common in UC and does not correlate with colonic disease activity. More than 50% of UC patients in remission showed active histological disease in the appendix. Favorable response to appendectomy for refractory UC was seen in cases with ulcerative appendicitis. These findings might support the role of the appendix as a pivotal organ in UC.
MeSH term(s)	Adult ; Appendectomy ; Appendicitis/complications ; Appendicitis/pathology ; Appendicitis/surgery ; Colitis, Ulcerative/complications ; Female ; Humans ; Male ; Middle Aged ; Prevalence ; Remission Induction
Language	English
Publishing date	2021-11-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2728585-6
ISSN	2050-6414 ; 2050-6406
ISSN (online)	2050-6414
ISSN	2050-6406
DOI	10.1002/ueg2.12171
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Article ; Online: Expression of MAdCAM-1 and Gut-homing T Cells in Inflamed Pouch Mucosa.

de Krijger, Manon / Wildenberg, Manon E / Mookhoek, Aart / Verheul, Sascha / de Jonge, Wouter J / Ponsioen, Cyriel Y

Journal of Crohn's & colitis

2021 Volume 15, Issue 9, Page(s) 1491–1499

Abstract: Background and aims: Pouchitis is a common complication following formation of an ileal pouch-anal anastomosis [IPAA] after proctocolectomy for ulcerative colitis [UC]. Gut-specific lymphocyte trafficking mechanisms have been identified as players in ... ...

Abstract	Background and aims: Pouchitis is a common complication following formation of an ileal pouch-anal anastomosis [IPAA] after proctocolectomy for ulcerative colitis [UC]. Gut-specific lymphocyte trafficking mechanisms have been identified as players in the pathogenesis of UC. In the present study, we aimed to characterise the presence of lymphocyte subsets expressing gut-homing molecules in pouches and peripheral blood of UC patients with and without pouchitis. Methods: Biopsy samples and peripheral blood were collected from 29 patients with an IPAA [seven with active inflammation, 22 without inflammation]. Expression of adhesion molecule MAdCAM-1 was assessed using immunohistochemistry, and flow cytometry was used to characterise expression of integrin α4β7, C-chemokine receptor 9 [CCR9], and CD103 on T cell subsets. Results: MAdCAM-1 expression was significantly increased in case of active inflammation in the pouch. T cells expressing integrin α4β7 were abundant in the pouch mucosa, but the frequency of integrin α4β7-expressing T cells was decreased on CD4+ lymphocytes during inflammation. Co-expression of gut-homing markers CCR9 and α4β7 was more pronounced in biopsies compared with peripheral blood, but was not enhanced upon active inflammation. Conclusions: Gut-homing T cells are abundant in pouch mucosa, but the classic hypothesis that the chronic inflammatory state is maintained by an accumulation of α4β7-expressing effector T cells is not supported by our data.
MeSH term(s)	Adult ; Antigens, CD/metabolism ; Case-Control Studies ; Cell Adhesion Molecules/metabolism ; Cohort Studies ; Colitis, Ulcerative/metabolism ; Colitis, Ulcerative/surgery ; Female ; Humans ; Integrin alpha Chains/metabolism ; Integrins/metabolism ; Male ; Middle Aged ; Mucoproteins/metabolism ; Pouchitis/etiology ; Pouchitis/metabolism ; Proctocolectomy, Restorative/adverse effects ; Receptors, CCR/metabolism ; T-Lymphocyte Subsets/metabolism
Chemical Substances	Antigens, CD ; CC chemokine receptor 9 ; Cell Adhesion Molecules ; Integrin alpha Chains ; Integrins ; MADCAM1 protein, human ; Mucoproteins ; Receptors, CCR ; alpha E integrins ; integrin alpha4beta7
Language	English
Publishing date	2021-03-03
Publishing country	England
Document type	Journal Article
ZDB-ID	2390120-2
ISSN	1876-4479 ; 1873-9946
ISSN (online)	1876-4479
ISSN	1873-9946
DOI	10.1093/ecco-jcc/jjab041
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Zs.A 6634: Show issues

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Article ; Online: House dust mite: a new player in intestinal inflammation?

Wildenberg, Manon E / van den Brink, Gijs R

Gut

2016 Volume 65, Issue 5, Page(s) 727–728

MeSH term(s)	Animals ; Asthma ; Humans ; Inflammation ; Pyroglyphidae
Language	English
Publishing date	2016-05
Publishing country	England
Document type	Comment ; Journal Article
ZDB-ID	80128-8
ISSN	1468-3288 ; 0017-5749
ISSN (online)	1468-3288
ISSN	0017-5749
DOI	10.1136/gutjnl-2015-311042
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Zs.A 160: Show issues

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Article ; Online: Recapitulating Suckling-to-Weaning Transition In Vitro using Fetal Intestinal Organoids.

Garcia, Tânia Martins / Navis, Marit / Wildenberg, Manon E / van Elburg, Ruurd M / Muncan, Vanesa

Journal of visualized experiments : JoVE

2019 , Issue 153

Abstract	At the end of the suckling period, many mammalian species undergo major changes in the intestinal epithelium that are associated with the capability to digest solid food. This process is termed suckling-to-weaning transition and results in the replacement of neonatal epithelium with adult epithelium which goes hand in hand with metabolic and morphological adjustments. These complex developmental changes are the result of a genetic program that is intrinsic to the intestinal epithelial cells but can, to some extent, be modulated by extrinsic factors. Prolonged culture of mouse primary intestinal epithelial cells from late fetal period, recapitulates suckling-to-weaning transition in vitro. Here, we describe a detailed protocol for mouse fetal intestinal organoid culture best suited to model this process in vitro. We describe several useful assays designed to monitor the change of intestinal functions associated with suckling-to-weaning transition over time. Additionally, we include an example of an extrinsic factor that is capable to affect suckling-to-weaning transition in vivo, as a representation of modulating the timing of suckling-to-weaning transition in vitro. This in vitro approach can be used to study molecular mechanisms of the suckling-to-weaning transition as well as modulators of this process. Importantly, with respect to animal ethics in research, replacing in vivo models by this in vitro model contributes to refinement of animal experiments and possibly to a reduction in the use of animals to study gut maturation processes.
MeSH term(s)	Animals ; Animals, Suckling/physiology ; Cells, Cultured ; Epithelial Cells/physiology ; Fetal Development/physiology ; Intestinal Mucosa/cytology ; Intestinal Mucosa/embryology ; Intestinal Mucosa/physiology ; Mice ; Organ Culture Techniques ; Organoids/cytology ; Organoids/embryology ; Organoids/physiology ; Weaning
Language	English
Publishing date	2019-11-15
Publishing country	United States
Document type	Journal Article ; Video-Audio Media
ZDB-ID	2259946-0
ISSN	1940-087X ; 1940-087X
ISSN (online)	1940-087X
ISSN	1940-087X
DOI	10.3791/60470
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