Type-2 cytokine-producing innate cells and IgE

（様式１）
学友会セミナー
申請日：
平成
26
年 6
月
2
日（月）
開催日時：平成
26
年 7
月
1
日（火）
11：00
～
12：00
開催場所：1 号館 2 階会議室
講師： Dr. Yui-Hsi Wang
所属・職名：Cincinnati Children's Hospital Medical Center, Assistant Professor
国名：U.S.A.
演題：Type-2 cytokine-producing innate cells and IgE-mediated food allergy
概要： IgE-mediated food allergy is manifested by an overactive T-helper 2 immune
response to dietary antigens in the gastrointestinal (GI) tract. Little is known about
the underlying mechanisms that initiate type-2 inflammatory response and drive
intestinal mastocytosis to develop experimental food allergy. We observe that IL-25
expression is rapidly elevated in the epithelial cells of inflamed duodenum at the
early phase of experimetnal food allergy. Mice overexpressing intestinal IL-25 are
more prone to develop gastrointestinal manifestations after repetitive intragastric
OVA challenge; on the contrary, mice deficient of IL-17RB, a cognate receptor for
IL-25, exhibited attenuated intestinal mastocytosis and incidence of anaphylaxis.
The findings that mice reconstituted with bone marrow deficient of type-2 innate
lymphoid cells (ILC2) are resistance to developing experimental food allergy
suggest a role of the resident IL-25-responding ILC2 in initiating intestinal allergic
inflammation. Additionally, we have identified the multifunctional IL-9-producing
intestinal mast cell precursors (IMCP9) that secrete prodigious amounts of TH2
cytokines and mast cell protease-1 (MCPt-1) in response to IL-33 and antigen/IgE
complex crosslinking, respectively. Repeated intragastric antigen challenge induces
significant accumulations of both IMCP9 and CD4+TH2 cell accumulation, which
correlate positively with symptoms and susceptibility to experimental food allergy.
Unlike the conventional mast cell lineage, IMCP9 development requires T cells and
IL-4/STAT6, not IL-9/IL-9R signals. Mice ablated of IMCP9 induction failed to
develop intestinal mastocytosis, which resulted in decreased food allergy symptoms
that could be restored by adoptively transferred IMCP9. Thus, we propose a
stepwise interaction between type-2 cytokine-producing gut resident ILC2 and
induced IMCP9 to initiate and amplify intestinal allergic inflammation, respectively,
that perpetuates the anaphylactic response to dietary proteins.
◯主たる世話人：清野
世話人：渡会
宏
（炎症免疫学分野
浩志（ステムセルバンク
教授）
特任准教授）

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