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B cell expansion hinders the stroma-epithelium regenerative cross talk during mucosal healing

Therapeutic promotion of intestinal regeneration holds great promise, but defining the cellular mechanisms that influence tissue regeneration remains an unmet challenge. To gain insight into the process of mucosal healing, we longitudinally examined the immune cell composition during intestinal dama...

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Main Authors: Frede, Annika (Author) , Czarnewski, Paulo (Author) , Monasterio, Gustavo (Author) , Tripathi, Kumar P. (Author) , Bejarano, David A. (Author) , Ramirez Flores, Ricardo O. (Author) , Sorini, Chiara (Author) , Larsson, Ludvig (Author) , Luo, Xinxin (Author) , Geerlings, Laura (Author) , Novella-Rausell, Claudio (Author) , Zagami, Chiara (Author) , Kuiper, Raoul (Author) , Morales, Rodrigo A. (Author) , Castillo, Francisca (Author) , Hunt, Matthew (Author) , Mariano, Livia Lacerda (Author) , Hu, Yue O. O. (Author) , Engblom, Camilla (Author) , Lennon-Duménil, Ana-Maria (Author) , Mittenzwei, Romy (Author) , Westendorf, Astrid M. (Author) , Hövelmeyer, Nadine (Author) , Lundeberg, Joakim (Author) , Sáez Rodríguez, Julio (Author) , Schlitzer, Andreas (Author) , Das, Srustidhar (Author) , Villablanca, Eduardo J. (Author)
Format: Article (Journal)
Language:English
Published: 13 December 2022
In: Immunity
Year: 2022, Volume: 55, Issue: 12, Pages: 2336-2351, e1-e12
ISSN:1097-4180
DOI:10.1016/j.immuni.2022.11.002
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.immuni.2022.11.002
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1074761322005921
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Author Notes:Annika Frede, Paulo Czarnewski, Gustavo Monasterio, Kumar P. Tripathi, David A. Bejarano, Ricardo O. Ramirez Flores, Chiara Sorini, Ludvig Larsson, Xinxin Luo, Laura Geerlings, Claudio Novella-Rausell, Chiara Zagami, Raoul Kuiper, Rodrigo A. Morales, Francisca Castillo, Matthew Hunt, Livia Lacerda Mariano, Yue O. O. Hu, Camilla Engblom, Ana-Maria Lennon-Duménil, Romy Mittenzwei, Astrid M. Westendorf, Nadine Hövelmeyer, Joakim Lundeberg, Julio Saez-Rodriguez, Andreas Schlitzer, Srustidhar Das, and Eduardo J. Villablanca
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Summary:Therapeutic promotion of intestinal regeneration holds great promise, but defining the cellular mechanisms that influence tissue regeneration remains an unmet challenge. To gain insight into the process of mucosal healing, we longitudinally examined the immune cell composition during intestinal damage and regeneration. B cells were the dominant cell type in the healing colon, and single-cell RNA sequencing (scRNA-seq) revealed expansion of an IFN-induced B cell subset during experimental mucosal healing that predominantly located in damaged areas and associated with colitis severity. B cell depletion accelerated recovery upon injury, decreased epithelial ulceration, and enhanced gene expression programs associated with tissue remodeling. scRNA-seq from the epithelial and stromal compartments combined with spatial transcriptomics and multiplex immunostaining showed that B cells decreased interactions between stromal and epithelial cells during mucosal healing. Activated B cells disrupted the epithelial-stromal cross talk required for organoid survival. Thus, B cell expansion during injury impairs epithelial-stromal cell interactions required for mucosal healing, with implications for the treatment of IBD.
Item Description:Online veröffentlicht am 2. Dezember 2022, Artikelversion vom 13. Dezember 2022
Gesehen am 28.11.2023
Physical Description:Online Resource
ISSN:1097-4180
DOI:10.1016/j.immuni.2022.11.002

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