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

J 2020

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

SUSHAMA JOSE, Shyam, Marco DE ZUANI, Federico TIDU, Marcela HORTOVÁ KOHOUTKOVÁ, Lucia PAZZAGLI et. al.

Basic information

Original name

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

Authors

SUSHAMA JOSE, Shyam (356 India), Marco DE ZUANI (380 Italy), Federico TIDU (380 Italy, belonging to the institution), Marcela HORTOVÁ KOHOUTKOVÁ (203 Czech Republic), Lucia PAZZAGLI (380 Italy), Giancarlo FORTE (380 Italy), Roberta SPACCAPELO (380 Italy), Teresa ZELANTE (380 Italy) and Jan FRIČ (203 Czech Republic, guarantor)

Edition

CLINICAL & TRANSLATIONAL IMMUNOLOGY, HOBOKEN, WILEY, 2020, 2050-0068

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30102 Immunology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 6.161

RIV identification code

RIV/00216224:14110/20:00116016

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.1002/cti2.1131

UT WoS

000537716300010

Keywords in English

immune response; infection; leucocyte migration; tissue organoids; Toll-like receptors

Abstract

V originále

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 'intermediate-like' 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.

Citovat

SUSHAMA JOSE, Shyam, Marco DE ZUANI, Federico TIDU, Marcela HORTOVÁ KOHOUTKOVÁ, Lucia PAZZAGLI, Giancarlo FORTE, Roberta SPACCAPELO, Teresa ZELANTE and Jan FRIČ. Comparison of two human organoid models of lung and intestinal inflammation reveals Toll-like receptor signalling activation and monocyte recruitment. CLINICAL & TRANSLATIONAL IMMUNOLOGY. HOBOKEN: WILEY, 2020, vol. 9, No 5, p. 1-15. ISSN 2050-0068. Available from: https://dx.doi.org/10.1002/cti2.1131.

@article{1670506,
   author = {Sushama Jose, Shyam and De Zuani, Marco and Tidu, Federico and Hortová Kohoutková, Marcela and Pazzagli, Lucia and Forte, Giancarlo and Spaccapelo, Roberta and Zelante, Teresa and Frič, Jan},
   article_location = {HOBOKEN},
   article_number = {5},
   doi = {http://dx.doi.org/10.1002/cti2.1131},
   keywords = {immune response; infection; leucocyte migration; tissue organoids; Toll-like receptors},
   language = {eng},
   issn = {2050-0068},
   journal = {CLINICAL & TRANSLATIONAL IMMUNOLOGY},
   title = {Comparison of two human organoid models of lung and intestinal inflammation reveals Toll-like receptor signalling activation and monocyte recruitment},
   url = {https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cti2.1131},
   volume = {9},
   year = {2020}
}

TY  - JOUR
ID  - 1670506
AU  - Sushama Jose, Shyam - De Zuani, Marco - Tidu, Federico - Hortová Kohoutková, Marcela - Pazzagli, Lucia - Forte, Giancarlo - Spaccapelo, Roberta - Zelante, Teresa - Frič, Jan
PY  - 2020
TI  - Comparison of two human organoid models of lung and intestinal inflammation reveals Toll-like receptor signalling activation and monocyte recruitment
JF  - CLINICAL & TRANSLATIONAL IMMUNOLOGY
VL  - 9
IS  - 5
SP  - 1-15
EP  - 1-15
PB  - WILEY
SN  - 20500068
KW  - immune response
KW  - infection
KW  - leucocyte migration
KW  - tissue organoids
KW  - Toll-like receptors
UR  - https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cti2.1131
L2  - https://onlinelibrary.wiley.com/doi/pdfdirect/10.1002/cti2.1131
N2  - 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 'intermediate-like' 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.
ER  -

SUSHAMA JOSE, Shyam, Marco DE ZUANI, Federico TIDU, Marcela HORTOVÁ KOHOUTKOVÁ, Lucia PAZZAGLI, Giancarlo FORTE, Roberta SPACCAPELO, Teresa ZELANTE and Jan FRIČ. Comparison of two human organoid models of lung and intestinal inflammation reveals Toll-like receptor signalling activation and monocyte recruitment. \textit{CLINICAL \&{} TRANSLATIONAL IMMUNOLOGY}. HOBOKEN: WILEY, 2020, vol.~9, No~5, p.~1-15. ISSN~2050-0068. Available from: https://dx.doi.org/10.1002/cti2.1131.

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