한빛사논문
- 조회227
Jinbo Yu 1 2, Vu Huy Hoang Duong 1 2, Katrin Westphal 1 2, Andreas Westphal 1 2, Abdulhadi Suwandi 3, Guntram A Grassl 3, Korbinian Brand 2, Andrew C Chan 4, Niko Föger 1 2, Kyeong-Hee Lee 1 2
1Inflammation Research Group.
2Institute of Clinical Chemistry, and.
3Institute of Medical Microbiology and Hospital Epidemiology and German Center for Infection Research (DZIF), Hannover Medical School, Hannover, Germany.
4Research, Genentech, South San Francisco, California, USA.
Address correspondence to: Kyeong-Hee Lee
JY and VHHD contributed equally to this work. NF and KHL are co–senior authors.
Abstract
The immune system is tightly controlled by regulatory processes that allow for the elimination of invading pathogens, while limiting immunopathological damage to the host. In the present study, we found that conditional deletion of the cell surface receptor Toso on B cells unexpectedly resulted in impaired proinflammatory T cell responses, which led to impaired immune protection in an acute viral infection model and was associated with reduced immunopathological tissue damage in a chronic inflammatory context. Toso exhibited its B cell-inherent immunoregulatory function by negatively controlling the pool of IL-10-competent B1 and B2 B cells, which were characterized by a high degree of self-reactivity and were shown to mediate immunosuppressive activity on inflammatory T cell responses in vivo. Our results indicate that Toso is involved in the differentiation/maintenance of regulatory B cells by fine-tuning B cell receptor activation thresholds. Furthermore, we showed that during influenza A-induced pulmonary inflammation, the application of Toso-specific antibodies selectively induced IL-10-competent B cells at the site of inflammation and resulted in decreased proinflammatory cytokine production by lung T cells. These findings suggest that Toso may serve as a novel therapeutic target to dampen pathogenic T cell responses via the modulation of IL-10-competent regulatory B cells.
논문정보
- Research article
- 2018년 05월 (BRIC 등록일 2022-12-08)
- 국외 연구진
- 의약학 > 면역의학
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