Efferocytosis induces a novel SLC program to promote glucose uptake and lactate release (Nature 2018, 563(7733):714-718)

報告日期: 2019/04/23
報告時間: 16:00/16:50
報告學生: 劉建聰(以英文報告)
講評老師: 蔣輯武
附件下載:

Efferocytosis induces a novel SLC program to promote glucose uptake and lactate release

Sho Morioka, et al.

Nature 2018, 563(7733):714-718

Presenter:Chien-Tsung Liu (劉建聰)       Date/Time: 2019/04/23 16:00-17:00

Commentator: Chi-Wu Chiang, PhD. (蔣輯武)            Location:Room 602

Background:

During development and aging, lots of cells are programmed to be eliminated via apoptosis to maintain tissue homeostasis. Corpses or apoptotic cells are engulfed and removed by either tissue-resident professional phagocytes or neighboring non-professional phagocytes thru efferocytosis.

Efferocytosis is divided into three steps, 1) Smell, phagocyte senses factors released by apoptotic cells. 2) Taste, phagocyte contacts to apoptotic cell. 3) Ingestion, phagocyte engulfs corpse. Different from antibody-mediated phagocytosis, efferocytosis does not induce inflammatory response.

Solute carrier (SLC) superfamily is a membrane transporter protein family. SLC proteins transport variant molecules, from small ion to metabolic intermediates.

Objective/Hypothesis:

How the molecular profiling changes in phagocytes during efferocytosis is incompletely understood

Results:

To investigate the gene expression changes during efferocytosis, the authors performed RNA-seq analysis and characterized specific SLC proteins that were regulated during different steps of efferocytosis. SLC2a1 and SLC16a1 were activated to promote glucose uptake and lactate release. With the increase of intracellular glucose, aerobic glycolysis was robustly elevated. Moreover, glycolysis activation within phagocyte further contributed to actin polymerization and enhanced corpse removal. Lactate secreting from phagocyte also established an anti-inflammatory tissue environment to suppress inflammatory response.

References:

1    Arandjelovic, S. & Ravichandran, K. S. Phagocytosis of apoptotic cells in homeostasis. Nat Immunol 16, 907-917, doi:10.1038/ni.3253 (2015).

2    Elliott, M. R. & Ravichandran, K. S. The Dynamics of Apoptotic Cell Clearance. Dev Cell 38, 147-160, doi:10.1016/j.devcel.2016.06.029 (2016).