東京大学医科学研究所

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学友会セミナー

学友会セミナー:2019年10月30日

開催日時: 2019年10月30日 16:00 ~ 17:30
開催場所: 1号館講堂
講師: Moshe Arditi
所属: Cedars-Sinai Medical Center・教授
演題: Intestinal permeability and IgA provoke immune vasculitis linked to cardiovascular inflammation
概要:

Kawasaki Disease (KD), a systemic vasculitis of unknown etiology is the leading cause of acquired heart disease among children in the US. Subsets of KD children display gastrointestinal abnormalities during the acute phase of the disease and may have increased serum levels of secretory IgA (SIgA), suggestive of a “leaky gut” phenotype. Additionally, KD patients have higher frequencies of IgA producing B cells in the inflamed coronary artery and in the respiratory and gastrointestinal tracts. How intestinal permeability participates in cardiovascular lesions of KD remains unknown. We observed increased intestinal permeability and elevated circulating sIgA in KD patients as well as elevated sIgA and IgA deposition in vascular tissues in the Lactobacillus casei-cell wall extract murine model of KD vasculitis. Pharmacological blocking of intestinal permeability prevented gut permeability, vascular tissues IgA deposition, and ameliorated cardiovascular pathology. By using genetic and pharmacologic inhibition of IL-1β signaling, we demonstrated that IL-1β lies upstream of disrupted intestinal barrier function, subsequent IgA vasculitis development, and cardiac inflammation. Thus, targeting mucosal barrier dysfunction and the IL-1β pathway may be applicable to other IgA-related diseases including IgA vasculitis and IgA nephropathy. These observations enhance our current understanding of KD pathogenesis and may provide new diagnostic and therapeutic strategies for affected patients.

世話人: 〇Cevayir COBAN (マラリア免疫学分野)
 石井 健 (ワクチン科学分野)