[Frontiers in Bioscience 14, 2631-2646, January 1, 2009]

[Frontiers in Bioscience 14, 2631-2646, January 1, 2009]

Tyro3 receptor tyrosine kinases in the heterogeneity of apoptotic cell uptake

Jeffrey L. Curtis, Jill C. Todt, Bin Hu, John J. Osterholzer, Christine M. Freeman

Pulmonary and Critical Care Medicine, Department of Veterans Affairs Healthsystem and University of Michigan Health System, Ann Arbor, MI 48105

TABLE OF CONTENTS

1. Abstract
2. Introduction - The importance of mononuclear phagocyte uptake of apoptotic cells
3. Heterogeneity of apoptotic cell uptake by mononuclear phagocytes: 3.1. Monocytes; 3.2. Resident tissue macrophages; 3.3. Dendritic cells
4. The Tyro3 family of receptor tyrosine kinases (RTKs): 4.1. Structure and function of Tyro3 RTKs; 4.2. Difference in Tyro3 RTK expression among mononuclear phagocyte subsets
5. Tyro3 RTKs as signal-transducing elements during apoptotic cell uptake: 5.1. Basics of signal-transduction during apoptotic cell uptake; 5.2. Features of Tyro3 RTKs that facilitate signal transduction; 5.3. What's so special about Tyro3 RTKs?
6. Conclusions
7. Acknowledgements
8. References

1. ABSTRACT

Mononuclear phagocytes comprise a mobile, broadly dispersed and highly adaptable system that lies at the very epicenter of host defense against pathogens and the interplay of the innate and adaptive arms of immunity. Understanding the molecular mechanisms that control the response of mononuclear phagocytes to apoptotic cells and the anti-inflammatory consequences of that response is an important goal with implications for multiple areas of biomedical sciences. This review details current understanding of the heterogeneity of apoptotic cell uptake by different members of the mononuclear phagocyte family in humans and mice. It also recounts the unique role of the Tyro3 family of receptor tyrosine kinases, best characterized for Mertk, in the signal transduction leading both to apoptotic cell ingestion and the anti-inflammatory effects that result.