PPAR-delta senses and orchestrates clearance of apoptotic cells to promote tolerance (Nat Med, 2009, 15:1266-1272)

報告日期: 2010/05/18
報告時間: 16:10/17:00
報告學生: 劉雅惠(英文報告)
講評老師: 林秋烽


PPAR-d senses and orchestrates clearance of apoptotic

cells to promote tolerance

Lata Mukundan et al.

Nat Medicine 2009, 15: 1266-72

Speaker: Ya-Hui Liu

Commentator: Dr. Chiou-Feng Lin

Time: 2009/10/06 17:10-18:00

Place: Room 602



Macrophages are professional eating cells for clearance of apoptotic cells. Well-controlled phagocytosis prevents the presentation of self antigen which potentiates autoimmunity. Molecules involved in the recognition and uptake of apoptotic cells by macrophages have been identified. However, the transcriptional regulation in macrophages to sense apoptotic cells is still unclear. In the present study, the authors found that the expression of PPAR-d was abundant in macrophages after feeding with apoptotic cells, but not with latex beads, necrotic cells or opsonized sheep blood cells. Clustering analysis of microarray data showed that the expression of opsonin genes was obviously downregulated in Ppard-/- macrophages. After pharmacologic activation of PPAR-d in wild-type macrophages, expression of opsonins and phagocytosis of apoptotic cells were enhanced in a PPAR-d-dependent manner. Moreover, PPAR-d deificient mice spontaneously developed autoimmune disease with high levels of autoantibodies, decreased secretion of the anti-inflammatory cytokine IL-10, and deposition of immunocomplex in the kidney. To summarize these findings, nuclear receptor PPAR-d may play a sensor of apoptotic cells which coordinates the expression of opsonins genes for the clearance of apoptotic cells in macrophages, ensuring immune tolerance to self antigens.



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