Comparison of two human organoid models of lung and intestinal inflammation reveals Toll-like receptor signalling activation and monocyte recruitment

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F20%3A00072917" target="_blank" >RIV/00159816:_____/20:00072917 - isvavai.cz</a>

Alternative codes found

RIV/00216224:14110/20:00116016 RIV/00023736:_____/20:00013013

Result on the web

<a href="https://onlinelibrary.wiley.com/doi/full/10.1002/cti2.1131" target="_blank" >https://onlinelibrary.wiley.com/doi/full/10.1002/cti2.1131</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1002/cti2.1131" target="_blank" >10.1002/cti2.1131</a>

Result language

angličtina

Original language name

Comparison of two human organoid models of lung and intestinal inflammation reveals Toll-like receptor signalling activation and monocyte recruitment

Original language description

Objectives The activation of immune responses in mucosal tissues is a key factor for the development and sustainment of several pathologies including infectious diseases and autoimmune diseases. However, translational research and personalised medicine struggle to advance because of the lack of suitable preclinical models that successfully mimic the complexity of human tissues without relying on in vivo mouse models. Here, we propose two in vitro human 3D tissue models, deprived of any resident leucocytes, to model mucosal tissue inflammatory processes. Methods We developed human 3D lung and intestinal organoids differentiated from induced pluripotent stem cells to model mucosal tissues. We then compared their response to a panel of microbial ligands and investigated their ability to attract and host human primary monocytes. Results Mature lung and intestinal organoids comprised epithelial (EpCAM(+)) and mesenchymal (CD73(+)) cells which responded to Toll-like receptor stimulation by releasing pro-inflammatory cytokines and expressing tissue inflammatory markers including MMP9, COX2 and CRP. When added to the organoid culture, primary human monocytes migrated towards the organoids and began to differentiate to an &apos;intermediate-like&apos; phenotype characterised by increased levels of CD14 and CD16. Conclusion We show that human mucosal organoids exhibit proper immune functions and successfully mimic an immunocompetent tissue microenvironment able to host patient-derived immune cells. Our experimental set-up provides a novel tool to tackle the complexity of immune responses in mucosal tissues which can be tailored to different human pathologies.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30102 - Immunology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2020

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

CLINICAL &amp; TRANSLATIONAL IMMUNOLOGY

ISSN

2050-0068

e-ISSN

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Volume of the periodical

9

Issue of the periodical within the volume

5

Country of publishing house

US - UNITED STATES

Number of pages

15

Pages from-to

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UT code for WoS article

000537716300010

EID of the result in the Scopus database

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