B cell-mediated regulatory mechanisms control tumor-promoting intestinal inflammation.
Cell Rep
; 40(2): 111051, 2022 07 12.
Article
em En
| MEDLINE
| ID: mdl-35830810
ABSTRACT
Mechanisms underlying tumor-promoting inflammatory processes in colitis-associated colorectal cancer (CAC) remain largely elusive. Here, we provide genetic evidence for distinct B cell-mediated immunoregulatory mechanisms that protect from chronic colitis versus CAC. We demonstrate an inherent capacity of interleukin-10 (IL-10)-producing B cells to differentiate into immunoglobulin A (IgA) plasma cells (PCs) upon Toll-like receptor (TLR) activation. Our data show that B cell-derived IL-10 is essential to limit pathogenic T helper type 1 (Th1)/Th17 T cell responses during chronic colitis, while IgA PCs derived from IL-10+ B cells are being implicated in restraining tumorigenesis during CAC. Formation of a tumor-protective intestinal environment was associated with clonal expansion of specific types of colonic IgA PCs and development of an altered microbiota that attenuated CAC. We thus propose that regulatory B cell-mediated immunomodulation entails temporal release of IL-10, which is superseded by the generation of specific IgA affecting the microbial community, thereby controlling chronic inflammation and tumorigenesis in a distinctive but interrelated manner.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Colite
/
Linfócitos B Reguladores
/
Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article