Intestinal stroma guides monocyte differentiation to macrophages through GM-CSF

Egle Kvedaraite (), Magda Lourda, Natalia Mouratidou, Tim Düking, Avinash Padhi, Kirsten Moll, Paulo Czarnewski, Indranil Sinha, Ioanna Xagoraris, Efthymia Kokkinou, Anastasios Damdimopoulos, Whitney Weigel, Olga Hartwig, Telma E. Santos, Tea Soini, Aline Acker, Nelly Rahkonen, Malin Flodström Tullberg, Emma Ringqvist, Marcus Buggert, Carl Jorns, Ulrik Lindforss, Caroline Nordenvall, Christopher T. Stamper, David Unnersjö-Jess, Mira Akber, Ruta Nadisauskaite, Jessica Jansson, Niels Vandamme, Chiara Sorini, Marijke Elise Grundeken, Helena Rolandsdotter, George Rassidakis, Eduardo J. Villablanca, Maja Ideström, Stefan Eulitz, Henrik Arnell, Jenny Mjösberg, Jan-Inge Henter and Mattias Svensson ()
Additional contact information
Egle Kvedaraite: Karolinska University Hospital
Magda Lourda: Karolinska University Hospital
Natalia Mouratidou: Karolinska University Hospital
Tim Düking: Miltenyi Biotec B.V. & Co. KG
Avinash Padhi: Karolinska University Hospital
Kirsten Moll: Karolinska University Hospital
Paulo Czarnewski: Stockholm University
Indranil Sinha: Karolinska Institutet
Ioanna Xagoraris: Karolinska University Hospital
Efthymia Kokkinou: Karolinska University Hospital
Anastasios Damdimopoulos: Karolinska Institutet
Whitney Weigel: Karolinska University Hospital
Olga Hartwig: Miltenyi Biotec B.V. & Co. KG
Telma E. Santos: Miltenyi Biotec B.V. & Co. KG
Tea Soini: Karolinska University Hospital
Aline Acker: Karolinska University Hospital
Nelly Rahkonen: Karolinska Institutet
Malin Flodström Tullberg: Karolinska University Hospital
Emma Ringqvist: Karolinska University Hospital
Marcus Buggert: Karolinska University Hospital
Carl Jorns: Karolinska University Hospital
Ulrik Lindforss: Karolinska Institutet
Caroline Nordenvall: Karolinska Institutet
Christopher T. Stamper: Karolinska University Hospital
David Unnersjö-Jess: Royal Institute of Technology
Mira Akber: Karolinska University Hospital
Ruta Nadisauskaite: Karolinska University Hospital
Jessica Jansson: Karolinska University Hospital
Niels Vandamme: VIB Single Cell Core, VIB
Chiara Sorini: Solna, Karolinska Institutet and University Hospital
Marijke Elise Grundeken: Karolinska Institutet
Helena Rolandsdotter: Södersjukhuset, Karolinska Institutet
George Rassidakis: Karolinska University Hospital
Eduardo J. Villablanca: Solna, Karolinska Institutet and University Hospital
Maja Ideström: Karolinska University Hospital
Stefan Eulitz: Miltenyi Biotec B.V. & Co. KG
Henrik Arnell: Karolinska University Hospital
Jenny Mjösberg: Karolinska University Hospital
Jan-Inge Henter: Karolinska Institutet
Mattias Svensson: Karolinska University Hospital

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Stromal cells support epithelial cell and immune cell homeostasis and play an important role in inflammatory bowel disease (IBD) pathogenesis. Here, we quantify the stromal response to inflammation in pediatric IBD and reveal subset-specific inflammatory responses across colon segments and intestinal layers. Using data from a murine dynamic gut injury model and human ex vivo transcriptomic, protein and spatial analyses, we report that PDGFRA+CD142−/low fibroblasts and monocytes/macrophages co-localize in the intestine. In primary human fibroblast-monocyte co-cultures, intestinal PDGFRA+CD142−/low fibroblasts foster monocyte transition to CCR2+CD206+ macrophages through granulocyte-macrophage colony-stimulating factor (GM-CSF). Monocyte-derived CCR2+CD206+ cells from co-cultures have a phenotype similar to intestinal CCR2+CD206+ macrophages from newly diagnosed pediatric IBD patients, with high levels of PD-L1 and low levels of GM-CSF receptor. The study describes subset-specific changes in stromal responses to inflammation and suggests that the intestinal stroma guides intestinal macrophage differentiation.

Date: 2024
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DOI: 10.1038/s41467-024-46076-3

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