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

• Published in: Immunity (Cambridge, Mass.) Vol. 55; no. 12; pp. 2336 - 2351.e12
• Main Authors: Frede, Annika, Czarnewski, Paulo, Monasterio, Gustavo, Tripathi, Kumar P., Bejarano, David A., Ramirez Flores, Ricardo O., Sorini, Chiara, Larsson, Ludvig, Luo, Xinxin, Geerlings, Laura, Novella-Rausell, Claudio, Zagami, Chiara, Kuiper, Raoul, Morales, Rodrigo A., Castillo, Francisca, Hunt, Matthew, Mariano, Livia Lacerda, Hu, Yue O.O., Engblom, Camilla, Lennon-Duménil, Ana-Maria, Mittenzwei, Romy, Westendorf, Astrid M., Hövelmeyer, Nadine, Lundeberg, Joakim, Saez-Rodriguez, Julio, Schlitzer, Andreas, Das, Srustidhar, Villablanca, Eduardo J.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 13.12.2022
• Subjects: Animals; B cell; Colitis; Disease Models, Animal; Epithelial Cells - metabolism; Epithelium; fibroblasts; inflammation; Intestinal Mucosa; mucosal healing; organoids; single cell; spatial transcriptomics; stromal cell; tissue repair; Wound Healing; stromal cell; B cell; single cell; fibroblasts; inflammation; spatial transcriptomics; organoids; epithelium; tissue repair; mucosal healing
• ISSN: 1074-7613; 1097-4180; 1097-4180
• DOI: 10.1016/j.immuni.2022.11.002

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. [Display omitted] •B cells are the dominant immune cell type during colonic mucosal healing (MH)•IFN-induced B cells are associated with injury and expand during MH•B cell depletion results in enhanced MH following intestinal injury•B cells impair the interactions between IEC and stromal cells during MH The cellular mechanisms controlling mucosal healing (MH) following injury are largely unknown. Using unbiased multi-parameter analysis, Frede and colleagues identified that B cells accumulate in the colonic damaged areas during MH. Surprisingly, B cells played detrimental roles during MH, as their presence hindered the interaction between epithelium and stroma.