Nature Communications (Feb 2024)
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 Van 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,
- Mattias Svensson
Affiliations
- Egle Kvedaraite
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Magda Lourda
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Natalia Mouratidou
- Pediatric Gastroenterology, Hepatology and Nutrition Unit, Astrid Lindgren Children’s Hospital, Karolinska University Hospital
- Tim Düking
- Miltenyi Biotec B.V. & Co. KG
- Avinash Padhi
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Kirsten Moll
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Paulo Czarnewski
- Science for Life Laboratory, Department of Biochemistry and Biophysics and National Bioinformatics Infrastructure Sweden, Stockholm University
- Indranil Sinha
- Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet
- Ioanna Xagoraris
- Department of Pathology and Cancer Diagnostics, Karolinska University Hospital
- Efthymia Kokkinou
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Anastasios Damdimopoulos
- Bioinformatics and Expression Analysis Core Facility, Department of Biosciences and Nutrition, Karolinska Institutet
- Whitney Weigel
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Olga Hartwig
- Miltenyi Biotec B.V. & Co. KG
- Telma E. Santos
- Miltenyi Biotec B.V. & Co. KG
- Tea Soini
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Aline Van Acker
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Nelly Rahkonen
- Integrated Cardio Metabolic Centre, Department of Medicine Huddinge, Karolinska Institutet
- Malin Flodström Tullberg
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Emma Ringqvist
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Marcus Buggert
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Carl Jorns
- Department of Transplantation Surgery, Karolinska University Hospital
- Ulrik Lindforss
- Department of Molecular Medicine and Surgery, Karolinska Institutet
- Caroline Nordenvall
- Department of Molecular Medicine and Surgery, Karolinska Institutet
- Christopher T. Stamper
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- David Unnersjö-Jess
- Science for Life Laboratory, Dept. of Applied Physics, Royal Institute of Technology
- Mira Akber
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Ruta Nadisauskaite
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Jessica Jansson
- Pediatric Gastroenterology, Hepatology and Nutrition Unit, Astrid Lindgren Children’s Hospital, Karolinska University Hospital
- Niels Vandamme
- VIB Single Cell Core, VIB
- Chiara Sorini
- Immunology and Allergy Unit, Department of Medicine, Solna, Karolinska Institutet and University Hospital
- Marijke Elise Grundeken
- Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institutet
- Helena Rolandsdotter
- Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet
- George Rassidakis
- Department of Pathology and Cancer Diagnostics, Karolinska University Hospital
- Eduardo J. Villablanca
- Immunology and Allergy Unit, Department of Medicine, Solna, Karolinska Institutet and University Hospital
- Maja Ideström
- Pediatric Gastroenterology, Hepatology and Nutrition Unit, Astrid Lindgren Children’s Hospital, Karolinska University Hospital
- Stefan Eulitz
- Miltenyi Biotec B.V. & Co. KG
- Henrik Arnell
- Pediatric Gastroenterology, Hepatology and Nutrition Unit, Astrid Lindgren Children’s Hospital, Karolinska University Hospital
- Jenny Mjösberg
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- Jan-Inge Henter
- Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet
- Mattias Svensson
- Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital
- DOI
- https://doi.org/10.1038/s41467-024-46076-3
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 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.
