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

First Author  Frede A Year  2022
Journal  Immunity Volume  55
Issue  12 Pages  2336-2351.e12
PubMed ID  36462502 Mgi Jnum  J:337187
Mgi Id  MGI:7413818 Doi  10.1016/j.immuni.2022.11.002
Citation  Frede A, et al. (2022) B cell expansion hinders the stroma-epithelium regenerative cross talk during mucosal healing. Immunity 55(12):2336-2351.e12
abstractText  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.
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