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第423回 難研セミナー

日 時: 2009年 6月24日(水)17:30~19:30

場 所: 臨床講堂?(医科新棟A:地下1階)

演 者: Ajay Chawla&s_comma; M.D.&s_comma; Ph.D.
(Assistant Professor of Medicine&s_comma; Stanford University&s_comma; School of Medicine)

演 題: PPARδ&s_comma; Apoptotic Cell Clearance and Autoimmunity

Macrophages rapidly engulf apoptotic cells to limit the release of noxious
cellular contents and to restrict autoimmune responses against self
antigens. Although factors participating in recognition and engulfment of
apoptotic cells have been identified&s_comma; the transcriptional basis for the
sensing and silently disposing of apoptotic cells is unknown. Here we show
that peroxisome proliferator activated receptor δ (PPARδ) is rapidly
induced when macrophages engulf apoptotic cells and functions as a
transcriptional sensor of dying cells. Genetic deletion of PPARδ
dramatically decreases expression of opsonins resulting in impairment of
apoptotic cell clearance and reduction in anti-inflammatory cytokine
production. This increases autoantibody production and predisposes PPARδ
deficient mice to autoimmune kidney disease&s_comma; a phenotype resembling the
human disease systemic lupus erythematosus. Thus&s_comma; PPARδ plays a pivotal
role in orchestrating the timely disposal of apoptotic cells by macrophages&s_comma;
ensuring that tolerance to self is maintained.

Nature Medicine 7:48-52&s_comma; 2001
Science 294:1866-70&s_comma; 2001
Science 302:453-457&s_comma; 2003
Cell Metabolism 4:13-24&s_comma; 2006
Nature 447:1116-20&s_comma; 2007
Cell Metabolism 6:496-507&s_comma; 2008
Nature Clin Pract Endo Metab 4:619-26&s_comma; 2008

連絡先: 分子代謝医学分野・小川佳宏(内線4931)
共 催: 病態細胞生物学分野・清水重臣教授(内線4692)