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開催日時::平成19年3月20日(火) 17:00~18:00

開催場所: 東大医科研アムジェンホール 大会議室

講 師: 中江 進 博士

所 属: 理化学研究所免疫・アレルギー科学総合研究センター

演 題:Mast cell-derived TNF promotes Th17 cell-dependent
neutrophil-dominant airway inflammation

概要:IL-17 can contribute to host defense and autoimmunity&s_comma; in part by
orchestrating neutrophil recruitment. IL-17 also has been implicated in
non-atopic asthma&s_comma; in which the airway inflammation can include many
neutrophils. We used ovalbumin-specific TCR-expressing C57BL/6-OTII mice to
characterize the roles of mast cells and T cells in a new model of antigen
(Ag)- and T cell-dependent airway neutrophilia. We found that Th17 cells and
mast cells&s_comma; but neither Th1 cells&s_comma; Th2 cells nor antibody/Ag/FcRg-signaling&s_comma;
contributed significantly to the Ag-dependent airway neutrophilia elicited
in this model. Indeed&s_comma; IFN-g significantly suppressed IL-17-dependent airway
neutrophilia in this setting. We detected no significant role for the
candidate mast cell products histamine&s_comma; PGD2&s_comma; LTB4&s_comma; CXCL10 or IL-16 in the
neutrophil infiltration elicited in this model. By contrast&s_comma; IL-18&s_comma; IL-1b
and TNF each contributed significantly to Th17 differentiation and the
development of Ag- and Th17 cell-mediated airway neutrophilia. Moreover&s_comma; we
found that IL-17 enhanced mast cell-TNF production in vitro and that mast
cell-associated TNF contributed significantly to Ag- and Th17 cell-mediated
airway neutrophilia in vivo. These findings establish that mast cells can
significantly enhance&s_comma; by antibody- and FcRggindependent mechanisms&s_comma; an Ag-
and Th17 cell-dependent inflammatory response that is characterized by
neutrophil recruitment to the affected site.

世話人: ○岩倉洋一郎 &s_comma; 清野 宏