公開セミナー

開催日時：平成 29 年 9 月 11 日（月）開催場所：４号館３階

16：00～17：00国際粘膜ワクチン開発研究センターセミナー室

講師：Meirav Pevsner-Fischer
所属・職名：Department of Immunology,Weizmann Institute of Science・Senior Intern
演題：Host-microbiome interactions in health and disease
概要：The gastrointestinal tract harbors one of the highest densities
of microorganisms on earth, encompassing more than 1000 bacterialspecies. The members of this microbial ecosystem, termed the microbiota,
outnumber the host cells by a factor of 10-100 and collectively encompass
1000-fold more genes than the host. This assembly of microorganisms andtheir genomes, termed the microbiome, is separated from the host by onlya single layer of epithelial cells. Many of the bacterial inhabitantsof the mammalian gut perform functions critical for host physiology,
but at the same time pose a threat of translocation into its sterile
intestinal milieu with ensuing pathologies. The full scope of these
profoundmicrobiota-driven

hostphysiologicalandpathologicalprocesses remains obscure. Tight regulation of the host-microbiota
niche is essential for maintaining a mutualistic relationship between
the host and its inhabitants. This crucial task is provided byspecialized immune and epithelial cell subsets that control thecomposition and local containment of the gut microbiome, while
preserving an ability to elicit a potent inflammatory response against
invading pathogens. Deciphering currently unknown molecular cues
governing mammalian and microbial communication networks bears criticalimportance in understanding mucosal homeostasis and initiation ofdisease.

主たる世話人：植松
世話人：清野宏智公開セミナー

開催日時：平成 29 年 9 月 11 日（月）開催場所：４号館３階

17：00～18：00国際粘膜ワクチン開発研究センターセミナー室

講師：Andrea Reboldi
所 属 ・ 職 名 ： Howard Hughes Medical Institute and Department ofMicrobiology and Immunology, University of California San Francisco・Assistant Professor
演題：Mechanisms controlling intestinal IgA production.
概要：Secretory immunoglobulin A (IgA) is made by intestinal plasma

cells and has roles both in protection from gut pathogens and inmaintaining homeostasis of intestinal commensals.
Peyer’s patches (PPs)— the major organized lymphoid tissues of thesmall intestine, numbering 100 to 200 in humans and 6 to 12 inmice— are the dominant source of IgA-producing cells.
PPs are unique compared to other secondary lymphoid tissues in theircontinual exposure to an enormous diversity of microbiome- andfood-derived antigens and in the types of pathogens they encounter.
Antigens are delivered to PPs by specialized microfold (M) epithelial
cells and they may be captured and presented by resident dendritic
cells (DCs).
In accord with their state of chronic microbial antigen exposure,PPs exhibit continual germinal center (GC) activity. These GCs not
only contribute to the generation of B cells and plasma cells
producing somatically mutated gut antigen-specific IgA antibodies
but have also been suggested to support non-specific antigen
diversification of the B-cell repertoire.
However, the cellular interactions necessary for IgA class switchingare poorly defined. Here we show that in mice, activated B cells use
the chemokine receptor CCR6 to access the subepithelial dome (SED)of PPs. There, B cells undergo prolonged interactions with SED

dendritic cells (DCs). PP IgA class switching requires innate
lymphoidcells,

which

promotelymphotoxin-b

receptor(LTbR)– dependent maintenance of DCs. PP DCs augment IgA production
by integrin avb8-mediated activation of transforming growth
factor– b (TGFb). In mice where B cells cannot access the SED, IgA
responses against oral antigen and gut commensals are impaired.
These studies establish the PP SED as a niche supporting DC– B cellinteractions needed for TGFb activation and induction of mucosal IgA
responses
主たる世話人：植松世話人：清野宏智