B cell expansion hinders the stroma-epithelium regenerative cross talk during mucosal healing
Abstract
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) re-vealed 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 re-modeling. 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 orga-noid survival. Thus, B cell expansion during injury impairs epithelial-stromal cell interactions required for mucosal healing, with implications for the treatment of IBD.
Más información
Título según WOS: | ID WOS:000914674500001 Not found in local WOS DB |
Título de la Revista: | IMMUNITY |
Volumen: | 55 |
Número: | 12 |
Editorial: | Cell Press |
Fecha de publicación: | 2022 |
Página de inicio: | 2336 |
Página final: | + |
DOI: |
10.1016/j.immuni.2022.11.002 |
Notas: | ISI |