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PMID:17442946

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Citation

Seitz, HM, Camenisch, TD, Lemke, G, Earp, HS and Matsushima, GK (2007) Macrophages and dendritic cells use different Axl/Mertk/Tyro3 receptors in clearance of apoptotic cells. J. Immunol. 178:5635-42

Abstract

The clearance of apoptotic cells is important for regulating tissue homeostasis, inflammation, and autoimmune responses. The absence of receptor tyrosine kinases (Axl, Mertk, and Tyro3) results in widespread accumulation of apoptotic cells and autoantibody production in mice. In this report, we examine the function of the three family members in apoptotic cell clearance by different phagocytic cell types. Mertk elimination nearly abolished macrophage apoptotic cell phagocytosis; elimination of Axl, Tyro3, or both, reduced macrophage phagocytosis by approximately half, indicating that these also play a role. In contrast, apoptotic cell clearance in splenic and bone marrow-derived dendritic cells (DCs) is prolonged compared with macrophages and relied primarily on Axl and Tyro3. The slower ingestion may be due to lower DC expression of Axl and Tyro3 or absence of GAS6 expression, a known ligand for this receptor family. In vivo, phagocytosis of apoptotic material by retinal epithelial cells required Mertk. Unlike macrophages, there did not appear to be any role for Axl or Tyro3 in retinal homeostasis. Likewise, clearance of apoptotic thymocytes in vivo was dramatically reduced in mertk(kd) mice, but was normal in axl/tyro3(-/-) mice. Thus, cell and organ type specificity is clearly delineated, with DCs relying on Axl and Tyro3, retina and thymus requiring Mertk, and macrophages exhibiting an interaction that involves all three family members. Surprisingly, in macrophages, tyrosine phosphorylation of Mertk in response to apoptotic cells is markedly diminished from axl/tyro3(-/-) mice, suggesting that the interactions of these receptors by heterodimerization may be important in some cells.

Links

PubMed

Keywords

Animals; Apoptosis/genetics; Apoptosis/immunology; Dendritic Cells/enzymology; Dendritic Cells/immunology; Dimerization; Homeostasis; Macrophages/enzymology; Macrophages/immunology; Mice; Mice, Mutant Strains; Oncogene Proteins/genetics; Oncogene Proteins/physiology; Phosphorylation; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/physiology; Receptor Protein-Tyrosine Kinases/genetics; Receptor Protein-Tyrosine Kinases/physiology; Retina/cytology; Retina/immunology; Thymus Gland/cytology; Thymus Gland/immunology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:TYRO3

acts_upstream_of_or_within

GO:0043277: apoptotic cell clearance

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:1347244

P

  • occurs_in:(EMAPA:32760)

Seeded From UniProt

complete

MOUSE:UFO

acts_upstream_of_or_within

GO:0043277: apoptotic cell clearance

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:104294

P

  • occurs_in:(EMAPA:32760)

Seeded From UniProt

complete

MOUSE:MERTK

acts_upstream_of_or_within

GO:0043277: apoptotic cell clearance

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2387768

P

  • occurs_in:(EMAPA:17172)

Seeded From UniProt

complete

MOUSE:MERTK

acts_upstream_of_or_within

GO:0043277: apoptotic cell clearance

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2387768

P

Seeded From UniProt

complete


See also

References

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