Editor’s Pick: TYRO3, AXL, and MERTK Receptor Tyrosine Kinases: Is There Evidence of Direct Involvement in Development and Onset of Sjögren’s Syndrome?

Diagnosis of Sjögren’s syndrome has been made difficult as it exhibits a similar symptomatology to other autoimmune conditions. This is just one aspect of the disorder that has frustrated attempts to better understand its genetic, environmental, and immunological basis. In the following paper, Wanchoo et al. provide some welcome headway by pointing to the failure of TAM receptor tyrosine kinase signalling as a potential cause underlying the development of Sjögren’s syndrome. This is an informative and important read that will no doubt provide researchers with an invaluable insight into the disease pathogenesis, and offer a step towards creating a better understanding of the syndrome.

Arun Wanchoo,1 Alexandria Voigt,1 Ammon B. Peck,1,2 *Cuong Q. Nguyen1-3

1. Department of Pathology and Infectious Diseases, College of Veterinary Medicine, University of Florida, Gainesville, Florida, USA
2. Center for Orphan Autoimmune Disorders, College of Dentistry, University of Florida, Gainesville, Florida, USA
3. Department of Oral Biology, College of Dentistry, University of Florida, Gainesville, Florida, USA
*Correspondence to nguyenc@ufl.edu

Disclosure: The authors have declared no conflicts of interest.
Received: 09.03.16 Accepted: 10.05.16
Citation: EMJ Rheumatol. 2016;3[1]:92-99.

Abstract

Sjögren’s syndrome (SjS) is a chronic, progressive, systemic, human autoimmune disease in which an auto-inflammatory process within the salivary and lacrimal glands results in loss of saliva and tear production, respectively. In-depth analyses of the autoimmune process in humans and animal models of SjS substantiates one of the more important pathoaetiological pathways: an increased level of glandular apoptosis and/or cell lysis. We have hypothesised that failure in clearance of dying cells by macrophages, dendritic cells, and neighbouring tissues results in a sustained innate inflammatory response that transitions to autoimmunity. Since the intrinsic inhibition of inflammation following phagocytosis of dying cells is a function of a family of three receptor tyrosine kinases (RTKs) known as the TAM (Tyro3, Axl, and Mertk), we put forward the following hypothesis: based on published information and analysis of our public microarray data, the failure of TAM RTK signalling, specifically in activating suppressor of cytokine signalling (SOCS) 1 and SOCS3 (which are inhibitors of immune responses), may lead to autoimmunity, and specifically, to SjS-like disease.

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