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Myeloid Cell-Specific Deletion of PDGFR-α Promotes Dysbiotic Intestinal Microbiota and thus Increased Colitis Susceptibility

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Myeloid Cell-Specific Deletion of PDGFR-α Promotes Dysbiotic Intestinal Microbiota and thus Increased Colitis Susceptibility. / Dörk, Ronja; Pelczar, Penelope; Shiri, Ahmad M; Volmari, Annika; Zierz, Elisabeth; Giannou, Anastasios; Böttcher, Marius; Bosurgi, Lidia; Huber, Samuel; Manthey, Carolin F.

In: J CROHNS COLITIS, Vol. 17, No. 11, 24.11.2023, p. 1858-1869.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Dörk, R, Pelczar, P, Shiri, AM, Volmari, A, Zierz, E, Giannou, A, Böttcher, M, Bosurgi, L, Huber, S & Manthey, CF 2023, 'Myeloid Cell-Specific Deletion of PDGFR-α Promotes Dysbiotic Intestinal Microbiota and thus Increased Colitis Susceptibility', J CROHNS COLITIS, vol. 17, no. 11, pp. 1858-1869. https://doi.org/10.1093/ecco-jcc/jjad103

APA

Dörk, R., Pelczar, P., Shiri, A. M., Volmari, A., Zierz, E., Giannou, A., Böttcher, M., Bosurgi, L., Huber, S., & Manthey, C. F. (2023). Myeloid Cell-Specific Deletion of PDGFR-α Promotes Dysbiotic Intestinal Microbiota and thus Increased Colitis Susceptibility. J CROHNS COLITIS, 17(11), 1858-1869. https://doi.org/10.1093/ecco-jcc/jjad103

Vancouver

Dörk R, Pelczar P, Shiri AM, Volmari A, Zierz E, Giannou A et al. Myeloid Cell-Specific Deletion of PDGFR-α Promotes Dysbiotic Intestinal Microbiota and thus Increased Colitis Susceptibility. J CROHNS COLITIS. 2023 Nov 24;17(11):1858-1869. https://doi.org/10.1093/ecco-jcc/jjad103

Bibtex

@article{41812607f76d4f92a6b87dbe78b626b8,
title = "Myeloid Cell-Specific Deletion of PDGFR-α Promotes Dysbiotic Intestinal Microbiota and thus Increased Colitis Susceptibility",
abstract = "BACKGROUND AND AIMS: The incidence of inflammatory bowel diseases [IBD] is steadily increasing, and thus the identification of new targets to improve therapy is a major goal. Growth factors of the PDGF family and their receptors are expressed early in intestinal development and are found in mononuclear cells and macrophages in adult tissues. Macrophages play a distinct role in the pathogenesis of IBD since their function is crucial to maintaining tolerance.METHODS: We aimed to study the role of myeloid expression of PDGFR-α in mediating intestinal homeostasis in mouse IBD and infectious models.RESULTS: Our results show that loss of myeloid PDGFR-α increases susceptibility to dextran saline sulphate-induced colitis. Accordingly, LysM-PDGFR-α-/- mice showed higher colitis scores, and reduced levels of anti-inflammatory macrophages compared to control mice. This effect was mediated via a pro-colitogenic microbiota, which developed in the absence of myeloid PDGFR-α and caused increased colitis susceptibility in gnotobiotic mice upon faecal microbiota transplantation compared to controls. Furthermore, LysM-PDGFR-α-/- mice had a leaky gut, accompanied by impaired phagocytosis, resulting in a severe barrier defect.CONCLUSIONS: Taken together, our results indicate a protective role for myeloid PDGFR-α in maintaining gut homeostasis by promoting a protective intestinal microbiota and providing an anti-inflammatory macrophage phenotype.",
keywords = "Mice, Animals, Gastrointestinal Microbiome, Colitis/pathology, Inflammatory Bowel Diseases/complications, Myeloid Cells/pathology, Anti-Inflammatory Agents/adverse effects, Dextran Sulfate, Disease Models, Animal, Mice, Inbred C57BL",
author = "Ronja D{\"o}rk and Penelope Pelczar and Shiri, {Ahmad M} and Annika Volmari and Elisabeth Zierz and Anastasios Giannou and Marius B{\"o}ttcher and Lidia Bosurgi and Samuel Huber and Manthey, {Carolin F}",
note = "{\textcopyright} The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn{\textquoteright}s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.",
year = "2023",
month = nov,
day = "24",
doi = "10.1093/ecco-jcc/jjad103",
language = "English",
volume = "17",
pages = "1858--1869",
journal = "J CROHNS COLITIS",
issn = "1873-9946",
publisher = "Elsevier",
number = "11",

}

RIS

TY - JOUR

T1 - Myeloid Cell-Specific Deletion of PDGFR-α Promotes Dysbiotic Intestinal Microbiota and thus Increased Colitis Susceptibility

AU - Dörk, Ronja

AU - Pelczar, Penelope

AU - Shiri, Ahmad M

AU - Volmari, Annika

AU - Zierz, Elisabeth

AU - Giannou, Anastasios

AU - Böttcher, Marius

AU - Bosurgi, Lidia

AU - Huber, Samuel

AU - Manthey, Carolin F

N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For permissions, please email: journals.permissions@oup.com.

PY - 2023/11/24

Y1 - 2023/11/24

N2 - BACKGROUND AND AIMS: The incidence of inflammatory bowel diseases [IBD] is steadily increasing, and thus the identification of new targets to improve therapy is a major goal. Growth factors of the PDGF family and their receptors are expressed early in intestinal development and are found in mononuclear cells and macrophages in adult tissues. Macrophages play a distinct role in the pathogenesis of IBD since their function is crucial to maintaining tolerance.METHODS: We aimed to study the role of myeloid expression of PDGFR-α in mediating intestinal homeostasis in mouse IBD and infectious models.RESULTS: Our results show that loss of myeloid PDGFR-α increases susceptibility to dextran saline sulphate-induced colitis. Accordingly, LysM-PDGFR-α-/- mice showed higher colitis scores, and reduced levels of anti-inflammatory macrophages compared to control mice. This effect was mediated via a pro-colitogenic microbiota, which developed in the absence of myeloid PDGFR-α and caused increased colitis susceptibility in gnotobiotic mice upon faecal microbiota transplantation compared to controls. Furthermore, LysM-PDGFR-α-/- mice had a leaky gut, accompanied by impaired phagocytosis, resulting in a severe barrier defect.CONCLUSIONS: Taken together, our results indicate a protective role for myeloid PDGFR-α in maintaining gut homeostasis by promoting a protective intestinal microbiota and providing an anti-inflammatory macrophage phenotype.

AB - BACKGROUND AND AIMS: The incidence of inflammatory bowel diseases [IBD] is steadily increasing, and thus the identification of new targets to improve therapy is a major goal. Growth factors of the PDGF family and their receptors are expressed early in intestinal development and are found in mononuclear cells and macrophages in adult tissues. Macrophages play a distinct role in the pathogenesis of IBD since their function is crucial to maintaining tolerance.METHODS: We aimed to study the role of myeloid expression of PDGFR-α in mediating intestinal homeostasis in mouse IBD and infectious models.RESULTS: Our results show that loss of myeloid PDGFR-α increases susceptibility to dextran saline sulphate-induced colitis. Accordingly, LysM-PDGFR-α-/- mice showed higher colitis scores, and reduced levels of anti-inflammatory macrophages compared to control mice. This effect was mediated via a pro-colitogenic microbiota, which developed in the absence of myeloid PDGFR-α and caused increased colitis susceptibility in gnotobiotic mice upon faecal microbiota transplantation compared to controls. Furthermore, LysM-PDGFR-α-/- mice had a leaky gut, accompanied by impaired phagocytosis, resulting in a severe barrier defect.CONCLUSIONS: Taken together, our results indicate a protective role for myeloid PDGFR-α in maintaining gut homeostasis by promoting a protective intestinal microbiota and providing an anti-inflammatory macrophage phenotype.

KW - Mice

KW - Animals

KW - Gastrointestinal Microbiome

KW - Colitis/pathology

KW - Inflammatory Bowel Diseases/complications

KW - Myeloid Cells/pathology

KW - Anti-Inflammatory Agents/adverse effects

KW - Dextran Sulfate

KW - Disease Models, Animal

KW - Mice, Inbred C57BL

U2 - 10.1093/ecco-jcc/jjad103

DO - 10.1093/ecco-jcc/jjad103

M3 - SCORING: Journal article

C2 - 37377226

VL - 17

SP - 1858

EP - 1869

JO - J CROHNS COLITIS

JF - J CROHNS COLITIS

SN - 1873-9946

IS - 11

ER -