ILC1 drive intestinal epithelial and matrix remodelling

Geraldine M. Jowett; Michael D.A. Norman; Tracy T.L. Yu; Patricia Rosell Arévalo; Dominique Hoogland; Suzette T. Lust; Emily Read; Eva Hamrud; Nick J. Walters; Umar Niazi; Matthew Wai Heng Chung; Daniele Marciano; Omer S. Omer; Tomasz Zabinski; Davide Danovi; Graham M. Lord; Jöns Hilborn; Nicholas D. Evans; Cécile A. Dreiss; Laurent Bozec; Oommen P. Oommen; Christian D. Lorenz; Ricardo M.P. da Silva; Joana F. Neves; Eileen Gentleman

doi:10.1038/s41563-020-0783-8

ILC1 drive intestinal epithelial and matrix remodelling

Geraldine M. Jowett, Michael D.A. Norman, Tracy T.L. Yu, Patricia Rosell Arévalo, Dominique Hoogland, Suzette T. Lust, Emily Read, Eva Hamrud, Nick J. Walters, Umar Niazi, Matthew Wai Heng Chung, Daniele Marciano, Omer S. Omer, Tomasz Zabinski, Davide Danovi, Graham M. Lord, Jöns Hilborn, Nicholas D. Evans, Cécile A. Dreiss, Laurent BozecOommen P. Oommen, Christian D. Lorenz, Ricardo M.P. da Silva, Joana F. Neves, Eileen Gentleman

BioMediTech

Tutkimustuotos: Artikkeli › Scientific › vertaisarvioitu

7 Sitaatiot (Scopus)

Abstrakti

Organoids can shed light on the dynamic interplay between complex tissues and rare cell types within a controlled microenvironment. Here, we develop gut organoid cocultures with type-1 innate lymphoid cells (ILC1) to dissect the impact of their accumulation in inflamed intestines. We demonstrate that murine and human ILC1 secrete transforming growth factor β1, driving expansion of CD44v6⁺ epithelial crypts. ILC1 additionally express MMP9 and drive gene signatures indicative of extracellular matrix remodelling. We therefore encapsulated human epithelial–mesenchymal intestinal organoids in MMP-sensitive, synthetic hydrogels designed to form efficient networks at low polymer concentrations. Harnessing this defined system, we demonstrate that ILC1 drive matrix softening and stiffening, which we suggest occurs through balanced matrix degradation and deposition. Our platform enabled us to elucidate previously undescribed interactions between ILC1 and their microenvironment, which suggest that they may exacerbate fibrosis and tumour growth when enriched in inflamed patient tissues.

Alkuperäiskieli	Englanti
Sivut	250–259
Sivumäärä	22
Julkaisu	Nature Materials
Vuosikerta	20
Varhainen verkossa julkaisun päivämäärä	2020
DOI - pysyväislinkit	https://doi.org/10.1038/s41563-020-0783-8
Tila	Julkaistu - 2021
OKM-julkaisutyyppi	A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Julkaisufoorumi-taso

Jufo-taso 3

!!ASJC Scopus subject areas

Chemistry(all)
Materials Science(all)
Condensed Matter Physics
Mechanics of Materials
Mechanical Engineering

Pääsy asiakirjaan

10.1038/s41563-020-0783-8

Siteeraa tätä

Jowett, G. M., Norman, M. D. A., Yu, T. T. L., Rosell Arévalo, P., Hoogland, D., Lust, S. T., Read, E., Hamrud, E., Walters, N. J., Niazi, U., Chung, M. W. H., Marciano, D., Omer, O. S., Zabinski, T., Danovi, D., Lord, G. M., Hilborn, J., Evans, N. D., Dreiss, C. A., ... Gentleman, E. (2021). ILC1 drive intestinal epithelial and matrix remodelling. Nature Materials, 20, 250–259. https://doi.org/10.1038/s41563-020-0783-8

@article{017f46568a8a48b3b3dc792a50d167fa,

title = "ILC1 drive intestinal epithelial and matrix remodelling",

abstract = "Organoids can shed light on the dynamic interplay between complex tissues and rare cell types within a controlled microenvironment. Here, we develop gut organoid cocultures with type-1 innate lymphoid cells (ILC1) to dissect the impact of their accumulation in inflamed intestines. We demonstrate that murine and human ILC1 secrete transforming growth factor β1, driving expansion of CD44v6+ epithelial crypts. ILC1 additionally express MMP9 and drive gene signatures indicative of extracellular matrix remodelling. We therefore encapsulated human epithelial–mesenchymal intestinal organoids in MMP-sensitive, synthetic hydrogels designed to form efficient networks at low polymer concentrations. Harnessing this defined system, we demonstrate that ILC1 drive matrix softening and stiffening, which we suggest occurs through balanced matrix degradation and deposition. Our platform enabled us to elucidate previously undescribed interactions between ILC1 and their microenvironment, which suggest that they may exacerbate fibrosis and tumour growth when enriched in inflamed patient tissues.",

author = "Jowett, {Geraldine M.} and Norman, {Michael D.A.} and Yu, {Tracy T.L.} and {Rosell Ar{\'e}valo}, Patricia and Dominique Hoogland and Lust, {Suzette T.} and Emily Read and Eva Hamrud and Walters, {Nick J.} and Umar Niazi and Chung, {Matthew Wai Heng} and Daniele Marciano and Omer, {Omer S.} and Tomasz Zabinski and Davide Danovi and Lord, {Graham M.} and J{\"o}ns Hilborn and Evans, {Nicholas D.} and Dreiss, {C{\'e}cile A.} and Laurent Bozec and Oommen, {Oommen P.} and Lorenz, {Christian D.} and {da Silva}, {Ricardo M.P.} and Neves, {Joana F.} and Eileen Gentleman",

year = "2021",

doi = "10.1038/s41563-020-0783-8",

language = "English",

volume = "20",

pages = "250–259",

journal = "Nature Materials",

issn = "1476-1122",

publisher = "Nature Publishing Group",

}

Jowett, GM, Norman, MDA, Yu, TTL, Rosell Arévalo, P, Hoogland, D, Lust, ST, Read, E, Hamrud, E, Walters, NJ, Niazi, U, Chung, MWH, Marciano, D, Omer, OS, Zabinski, T, Danovi, D, Lord, GM, Hilborn, J, Evans, ND, Dreiss, CA, Bozec, L, Oommen, OP, Lorenz, CD, da Silva, RMP, Neves, JF & Gentleman, E 2021, 'ILC1 drive intestinal epithelial and matrix remodelling', Nature Materials, Vuosikerta 20, Sivut 250–259. https://doi.org/10.1038/s41563-020-0783-8

TY - JOUR

T1 - ILC1 drive intestinal epithelial and matrix remodelling

AU - Jowett, Geraldine M.

AU - Norman, Michael D.A.

AU - Yu, Tracy T.L.

AU - Rosell Arévalo, Patricia

AU - Hoogland, Dominique

AU - Lust, Suzette T.

AU - Read, Emily

AU - Hamrud, Eva

AU - Walters, Nick J.

AU - Niazi, Umar

AU - Chung, Matthew Wai Heng

AU - Marciano, Daniele

AU - Omer, Omer S.

AU - Zabinski, Tomasz

AU - Danovi, Davide

AU - Lord, Graham M.

AU - Hilborn, Jöns

AU - Evans, Nicholas D.

AU - Dreiss, Cécile A.

AU - Bozec, Laurent

AU - Oommen, Oommen P.

AU - Lorenz, Christian D.

AU - da Silva, Ricardo M.P.

AU - Neves, Joana F.

AU - Gentleman, Eileen

PY - 2021

Y1 - 2021

N2 - Organoids can shed light on the dynamic interplay between complex tissues and rare cell types within a controlled microenvironment. Here, we develop gut organoid cocultures with type-1 innate lymphoid cells (ILC1) to dissect the impact of their accumulation in inflamed intestines. We demonstrate that murine and human ILC1 secrete transforming growth factor β1, driving expansion of CD44v6+ epithelial crypts. ILC1 additionally express MMP9 and drive gene signatures indicative of extracellular matrix remodelling. We therefore encapsulated human epithelial–mesenchymal intestinal organoids in MMP-sensitive, synthetic hydrogels designed to form efficient networks at low polymer concentrations. Harnessing this defined system, we demonstrate that ILC1 drive matrix softening and stiffening, which we suggest occurs through balanced matrix degradation and deposition. Our platform enabled us to elucidate previously undescribed interactions between ILC1 and their microenvironment, which suggest that they may exacerbate fibrosis and tumour growth when enriched in inflamed patient tissues.

AB - Organoids can shed light on the dynamic interplay between complex tissues and rare cell types within a controlled microenvironment. Here, we develop gut organoid cocultures with type-1 innate lymphoid cells (ILC1) to dissect the impact of their accumulation in inflamed intestines. We demonstrate that murine and human ILC1 secrete transforming growth factor β1, driving expansion of CD44v6+ epithelial crypts. ILC1 additionally express MMP9 and drive gene signatures indicative of extracellular matrix remodelling. We therefore encapsulated human epithelial–mesenchymal intestinal organoids in MMP-sensitive, synthetic hydrogels designed to form efficient networks at low polymer concentrations. Harnessing this defined system, we demonstrate that ILC1 drive matrix softening and stiffening, which we suggest occurs through balanced matrix degradation and deposition. Our platform enabled us to elucidate previously undescribed interactions between ILC1 and their microenvironment, which suggest that they may exacerbate fibrosis and tumour growth when enriched in inflamed patient tissues.

U2 - 10.1038/s41563-020-0783-8

DO - 10.1038/s41563-020-0783-8

M3 - Article

AN - SCOPUS:85090432530

SN - 1476-1122

VL - 20

SP - 250

EP - 259

JO - Nature Materials

JF - Nature Materials

ER -

ILC1 drive intestinal epithelial and matrix remodelling

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