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Mediators of Inflammation
Volume 2017, Article ID 6848430, 13 pages
https://doi.org/10.1155/2017/6848430
Research Article

Growth Arrest-Specific 6 Enhances the Suppressive Function of CD4+CD25+ Regulatory T Cells Mainly through Axl Receptor

1Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China
2Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, China
3Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China

Correspondence should be addressed to Yong-Ming Yao; moc.anis@ff_c and Zhong-qiu Lu; moc.361@518046_qzl

Received 8 September 2016; Revised 7 November 2016; Accepted 5 December 2016; Published 8 February 2017

Academic Editor: Eugenio A. C. Silva

Copyright © 2017 Guang-ju Zhao et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background. Growth arrest-specific (Gas) 6 is one of the endogenous ligands of TAM receptors (Tyro3, Axl, and Mertk), and its role as an immune modulator has been recently emphasized. Naturally occurring CD4+CD25+ regulatory T cells (Tregs) are essential for the active suppression of autoimmunity. The present study was designed to investigate whether Tregs express TAM receptors and the potential role of Gas6-TAM signal in regulating the suppressive function of Tregs. Methods. The protein and mRNA levels of TAM receptors were determined by using Western blot, immunofluorescence, flow cytometry, and RT-PCR. Then, TAM receptors were silenced using targeted siRNA or blocked with specific antibody. The suppressive function of Tregs was assessed by using a CFSE-based T cell proliferation assay. Flow cytometry was used to determine the expression of Foxp3 and CTLA4 whereas cytokines secretion levels were measured by ELISA assay. Results. Tregs express both Axl and Mertk receptors. Gas6 increases the suppressive function of Tregs in vitro and in mice. Both Foxp3 and CTLA-4 expression on Tregs are enhanced after Gas6 stimulation. Gas6 enhances the suppressive activity of Tregs mainly through Axl receptor. Conclusion. Gas6 has a direct effect on the functions of CD4+CD25+Tregs mainly through its interaction with Axl receptor.