• 淋巴细胞活化信号分子家族成员4(SLAMF4)是肠道免疫的调节器,是小鼠和人类肠道免疫细胞的一种选择性标记物;
  • 在肠黏膜中,SLAMF4无需肠道相关淋巴组织的参与就可被直接诱导产生;
  • 肠道细菌尤其是厌氧菌的产物,以及肠道定殖抗原提呈细胞(APC)^TNLG8A是诱导SLAMF4的关键参与者;
  • SLAMF4表达的缺失,增强小鼠对口服病原体感染的易感性,并最终导致过早死亡。
蓝灿辉 | 热心肠先生
Gut [IF:19.819]

Gut symbiotic microbes imprint intestinal immune cells with the innate receptor SLAMF4 which contributes to gut immune protection against enteric pathogens



2017-03-24, Article

Abstract & Authors:展开

BACKGROUND: Interactions between host immune cells and gut microbiota are crucial for the integrity and function of the intestine. How these interactions regulate immune cell responses in the intestine remains a major gap in the field.
AIM: We have identified the signalling lymphocyte activation molecule family member 4 (SLAMF4) as an immunomodulator of the intestinal immunity. The aim is to determine how SLAMF4 is acquired in the gut and what its contribution to intestinal immunity is.
METHODS: Expression of SLAMF4 was assessed in mice and humans. The mechanism of induction was studied using GFP bone marrow chimaera mice, lymphotoxin α and TNLG8A-deficient mice, as well as gnotobiotic mice. Role in immune protection was revealed using oral infection with and .
RESULTS: SLAMF4 is a selective marker of intestinal immune cells of mice and humans. SLAMF4 induction occurs directly in the intestinal mucosa without the involvement of the gut-associated lymphoid tissue. Gut bacterial products, particularly those of gut anaerobes, and gut-resident antigen-presenting cell (APC) are key contributors of SLAMF4 induction in the intestine. Importantly, lack of SLAMF4 expression leads the increased susceptibility of mice to infection by oral pathogens culminating in their premature death.
CONCLUSIONS: SLAMF4 is a marker of intestinal immune cells which contributes to the protection against enteric pathogens and whose expression is dependent on the presence of the gut microbiota. This discovery provides a possible mechanism for answering the long-standing question of how the intertwining of the host and gut microbial biology regulates immune cell responses in the gut.

First Authors:
Allison Cabinian

Correspondence Authors:
Amale Laouar

All Authors:
Allison Cabinian,Daniel Sinsimer,May Tang,Youngsoon Jang,Bongkum Choi,Yasmina Laouar,Amale Laouar