title: Growth Arrest-Specific 6 Enhances the Suppressive Function of CD4+CD25+Regulatory T Cells Mainly through Axl Receptor.
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.
authors.affiliation: Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Guang-Ju
authors.initials: GJ
authors.lastname: Zhao
authors.affiliation: Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, China.
authors.forename: Jia-Yi
authors.initials: JY
authors.lastname: Zheng
authors.affiliation: Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Jia-Lan
authors.initials: JL
authors.lastname: Bian
authors.affiliation: Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Long-Wang
authors.initials: LW
authors.lastname: Chen
authors.affiliation: Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Dong
authors.affiliation: Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Guang-Liang
authors.initials: GL
authors.lastname: Hong
authors.affiliation: Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Arvine
authors.initials: A
authors.lastname: Chandoo
authors.affiliation: Burns Institute, First Hospital Affiliated to the Chinese PLA General Hospital, Beijing 100048, China.
authors.forename: Yong-Ming
authors.identifier: 0000-0002-3564-4012
authors.initials: YM
authors.lastname: Yao
authors.affiliation: Emergency Department, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Zhong-Qiu
authors.identifier: 0000-0002-0569-4182
authors.initials: ZQ
authors.lastname: Lu
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D051858:Forkhead Transcription Factors / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000378:metabolism*; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6
chemical_list: D051858:Forkhead Transcription Factors; D036341:Intercellular Signaling Peptides and Proteins; D053645:Interleukin-2 Receptor alpha Subunit; D011518:Proto-Oncogene Proteins; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase; D000099255:Growth Arrest-Specific Protein 6; C000722290:AXL receptor tyrosine kinase, mouse