Apoptotic neutrophils and T cells sequester chemokines during immune response resolution through modulation of CCR5 expression

Nature Immunology 7, 1209-1216 (2006)

Speaker: 鄭元鈞                              Place: Room 601

Commentator: 林秋烽老師                     Date: 2006/11/15 15:00~16:00

Abstract:

Acute inflammation is a complex reaction to injurious agents such as microbes.  During early phase of acute inflammation, a large numbers of leukocytes are directed to inflammation site for immune response by chemokines.  During resolution phase of inflammation, leukocytes undergo apoptosis and are cleared by phagocytes to limit inflammation.  Previous findings showed that deficiency in apoptotic cell clearance would result in the development of autoimmune.  CCL3, CCL4, CCL5 chemokines are important proinflammmatory mediators.  Their receptor CCR5 is involved in leukocytes and T cells trafficking in inflammation.  In this paper, the author discovered that CCR5 expressed on apoptotic neutrophils and T cells played an important role in scavenging CCR3 and CCR5 chemokines during resolution.  During this process, CCR5 expression on apoptotic cells was upregulated by the proresolution lipid mediators and cytokines such as lipoxin A4 and TGF-β and downregulated by proinflammatory cytokines such as TNF.  In addition, late apoptotic cells also had more CCR5 expression and stronger binding to CCL4 than healthy cells.  The author thus proposed that CCR5 on the surface of apoptotic leukocytes is an important mediator to mediate chemokines scavenging during resolution.  Before apoptotic cells are engulfed by macrophages, these dying cells appear to turn up the expression of CCR5 and help to terminate chmokine signaling.

References

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