Age-related changes in expression and signaling of TAM receptor inflammatory regulators in monocytes

Xiaomei Wang; Anna Malawista; Feng Qian; Christine Ramsey; Heather G. Allore; Ruth R. Montgomery

doi:10.18632/oncotarget.23851

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Research Papers: Gerotarget (Focus on Aging):

Age-related changes in expression and signaling of TAM receptor inflammatory regulators in monocytes

Xiaomei Wang _, Anna Malawista, Feng Qian, Christine Ramsey, Heather G. Allore and Ruth R. Montgomery

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Oncotarget. 2018; 9:9572-9580. https://doi.org/10.18632/oncotarget.23851

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Abstract

Xiaomei Wang1,*, Anna Malawista1,*, Feng Qian1,4, Christine Ramsey2, Heather G. Allore1 and Ruth R. Montgomery1,3

1Department of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut

2Yale Center for Medical Informatics, Yale University School of Medicine, New Haven, Connecticut

3Human Translational Immunology, Yale University School of Medicine, New Haven, Connecticut

4State Key Laboratory of Genetic Engineering and Ministry of Education Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China

*These authors contributed equally to this work

Correspondence to:

Ruth R. Montgomery, email: [email protected]

Keywords: 5 immunosenescence; monocyte; age-related immune dysregulation; TAM receptors; protein S; Gerotarget

Received: September 04, 2017 Accepted: October 25, 2017 Published: January 03, 2018

ABSTRACT

The multifactorial immune deterioration in aging --termed “inflamm-aging”--is comprised of a state of low-grade, chronic inflammation and complex dysregulation of responses to immune stimulation. The TAM family (Tyro 3, Axl, and Mer) of receptor tyrosine kinases are negative regulators of Toll like receptor-mediated immune responses that broadly inhibit cytokine receptor cascades to inhibit inflammation. Here we demonstrate elevated expression of TAM receptors in monocytes of older adults, and an age-dependent difference in signaling mediator AKT resulting in dysregulated responses to signaling though Mer. Our results may be especially significant in tissue, where levels of Mer are highest, and may present avenues for modulation of chronic tissue inflammation noted in aging.

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Research Papers: Gerotarget (Focus on Aging):

Age-related changes in expression and signaling of TAM receptor inflammatory regulators in monocytes

Abstract