한빛사논문
- 조회437
Christian Melcher1,2,7, Jinbo Yu1,2,7, Vu Huy Hoang Duong1,2,7, Katrin Westphal1,2,7, Noushin Helmi Siasi Farimany1,2, Anton Shaverskyi1,2, Bei Zhao3,4, Till Strowig3,4, Silke Glage5, Korbinian Brand2, Andrew C. Chan6, Niko Föger1,2,8, Kyeong-Hee Lee1,2,8,9
1Inflammation Research Group, Hannover Medical School, 30625 Hannover, Germany
2Institute of Clinical Chemistry, Hannover Medical School, 30625 Hannover, Germany
3Department of Microbial Immune Regulation, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany
4Hannover Medical School, 30625 Hannover, Germany
5Experimental Pathology, Institute for Laboratory Animal Science, Hannover Medical School, 30625 Hannover, Germany
6Research, Genentech, 1 DNA Way, South San Francisco, CA 94080, USA
7These authors contributed equally
8Senior author
9Lead contact
Corresponding author : Kyeong-Hee Lee
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 We thus propose that regulatory B cell-mediated immunomodulation entails temporal release of IL-10, which is superseded by the generation of specific IgA affecting the microbial community, thereby controlling chronic inflammation and tumorigenesis in a distinctive but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.
논문정보
- Research article
- 2022년 07월 (BRIC 등록일 2022-12-08)
- 국외 연구진
- 의약학 > 면역의학
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