title: Glucose-Regulated Protein 78-Induced Myeloid Antigen-Presenting Cells Maintained Tolerogenic Signature upon LPS Stimulation.
abstract: The 78-kDa glucose-regulated protein (Grp78) is stress-inducible chaperone that mostly reside in the endoplasmic reticulum. Grp78 has been described to be released at times of cellular stress and as having extracellular properties that are anti-inflammatory or favor the resolution of inflammation. As antigen-presenting cells (APCs) play a critical role in both the priming of adaptive immune responses and the induction of self-tolerance, herein, we investigated the effect of Grp78 on the maturation of murine myeloid APCs (CD11c+cells). Results showed that CD11c+cells could be bound by AF488-labeled Grp78 and that Grp78 treatment induced a tolerogenic phenotype comparable to immature cells. Furthermore, when exposed to lipopolysaccharide, Grp78-treated CD11c+cells (DCGrp78) did not adopt a mature dendritic cell phenotype. DCGrp78-primed T cells exhibited reduced proliferation along with a concomitant expansion of CD4+CD25+FoxP3+cells in pancreaticoduodenal lymph nodes and induction of T cell apoptosisin vitroandex vivo. The above work suggests that Grp78 is an immunomodulatory molecule that could aid resolution of inflammation. It may thus contribute to induce durable tolerance to be of potential therapeutic benefit in transplanted allogeneic grafts and autoimmune diseases such as type I diabetes.
authors.affiliation: Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Infectious Disease, Institute of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Muyang
authors.initials: M
authors.lastname: Yang
authors.affiliation: Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Kai
authors.initials: K
authors.lastname: Qin
authors.affiliation: Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Min
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Heli
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Huifen
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Infectious Disease, Institute of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Ning
authors.affiliation: Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Ping
authors.initials: P
authors.lastname: Lei
authors.affiliation: Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology , Wuhan , China.
authors.forename: Guanxin
authors.initials: G
authors.lastname: Shen
keywords: antigen-presenting cells; autoimmune disease; glucose-regulated protein 78; immune regulation; regulatory T cell