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ILC1 drive intestinal epithelial and matrix remodelling

ILC1 drive intestinal epithelial and matrix remodelling
ILC1 drive intestinal epithelial and matrix remodelling
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.
1476-1122
250-259
Jowett, Geraldine M.
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Norman, Michael D. A.
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Yu, Tracy T. L.
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Rosell Arévalo, Patricia
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Hoogland, Dominique
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Lust, Suzette T.
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Read, Emily
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Hamrud, Eva
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Walters, Nick J.
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Niazi, Umar
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Chung, Matthew Wai Heng
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Marciano, Daniele
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Omer, Omer S.
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Zabinski, Tomasz
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Danovi, Davide
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Lord, Graham M.
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Hilborn, Jöns
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Evans, Nicholas D.
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Dreiss, Cécile A.
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Bozec, Laurent
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Oommen, Oommen P.
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Lorenz, Christian D.
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Da Silva, Ricardo M. P.
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Neves, Joana F.
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Gentleman, Eileen
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Jowett, Geraldine M.
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Norman, Michael D. A.
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Yu, Tracy T. L.
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Rosell Arévalo, Patricia
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Hoogland, Dominique
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Lust, Suzette T.
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Read, Emily
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Hamrud, Eva
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Walters, Nick J.
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Niazi, Umar
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Chung, Matthew Wai Heng
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Marciano, Daniele
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Omer, Omer S.
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Zabinski, Tomasz
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Danovi, Davide
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Lord, Graham M.
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Hilborn, Jöns
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Evans, Nicholas D.
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Dreiss, Cécile A.
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Bozec, Laurent
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Oommen, Oommen P.
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Lorenz, Christian D.
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Da Silva, Ricardo M. P.
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Neves, Joana F.
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Gentleman, Eileen
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Jowett, Geraldine M., Norman, Michael D. A., Yu, Tracy T. L., Rosell Arévalo, Patricia, Hoogland, Dominique, Lust, Suzette T., Read, Emily, Hamrud, Eva, Walters, Nick J., Niazi, Umar, Chung, Matthew Wai Heng, Marciano, Daniele, Omer, Omer S., Zabinski, Tomasz, Danovi, Davide, Lord, Graham M., Hilborn, Jöns, Evans, Nicholas D., Dreiss, Cécile A., Bozec, Laurent, Oommen, Oommen P., Lorenz, Christian D., Da Silva, Ricardo M. P., Neves, Joana F. and Gentleman, Eileen (2020) ILC1 drive intestinal epithelial and matrix remodelling. Nature Materials, 20, 250-259. (doi:10.1038/s41563-020-0783-8).

Record type: Article

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.

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ILC1 Nat Mat author version_compressed - Accepted Manuscript
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More information

Accepted/In Press date: 23 July 2020
e-pub ahead of print date: 7 September 2020
Published date: 7 September 2020

Identifiers

Local EPrints ID: 444292
URI: http://eprints.soton.ac.uk/id/eprint/444292
ISSN: 1476-1122
PURE UUID: 476fdbcc-7a2d-4e82-b38b-2684cd622885

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Date deposited: 09 Oct 2020 16:32
Last modified: 18 Jun 2021 04:01

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Contributors

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

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