[대학원 생명과학과 세미나 안내]
연사 : 박주홍 교수 (서울대학교 생명과학부)
연제 : Regulation of inflammation at the interface of host-microbial symbiosis
일시 : 2019년 5월 31일 (금) 오후 5시
장소 : 하나과학관 A동 B131호
초청교수 : 이은진 교수
The mammalian gastrointestinal tract accommodates trillions of bacteria, many of which provide beneficial effects to the host. However, the intestinal immune system needs to adapt to the constantly fluctuating microbial environment at mucosal surfaces in order to maintain homeostasis. Changes in the microbiome can result in the dysregulation of the host immune system and increased susceptibility to inflammatory diseases. The mechanism by which the microbiome regulates intestinal immune responses remains unclear.
The microbiome induces the generation of intestinal regulatory T cells (Tregs) that express the nuclear hormone receptor RORγt. The differentiation of RORγt+ Tregs is dependent on bacterial antigen presentation by dendritic cells. RORγt+ Tregs share similar differentiation pathways with pro-inflammatory Th17, but the vitamin A metabolite retinoic acid promotes the differentiation of RORγt+ Tregs over Th17. RORγt+ Tregs regulate intestinal type 2 immune responses through altering the function of dendritic cells, thereby maintaining immune homeostasis at mucosal surfaces.
Microbe-associated molecular patterns (MAMPs) also regulate intestinal immune responses through Toll-like receptor signalling pathways. To explore the impact of MAMPs on the intestinal mucosal surface, we have generated a transgenic mouse model expressing flagellin in intestinal epithelial cells. Epithelial expression of flagellin promotes anti-inflammatory responses in a TLR5-dependent way. However, flagellin facilitates pro-inflammatory responses upon intestinal tissue injury. Therefore, flagellin promotes pro- or anti-inflammatory immune responses depending on the state of the intestinal epithelium, suggesting that MAMP-PRR signaling can be interpreted by the host immune system, selectively leading to symbiosis or pathogenesis.
Collectively, these results demonstrate that the gut microbiome has the ability to induce anti-inflammatory immune responses to establish homeostasis and symbiosis at the intestinal mucosal surface.