title: Grouping annotations on the subcellular layered interactome demonstrates enhanced autophagy activity in a recurrent experimental autoimmune uveitis T cell line.
abstract: Human uveitis is a type of T cell-mediated autoimmune disease that often shows relapse-remitting courses affecting multiple biological processes. As a cytoplasmic process, autophagy has been seen as an adaptive response to cell death and survival, yet the link between autophagy and T cell-mediated autoimmunity is not certain. In this study, based on the differentially expressed genes (GSE19652) between the recurrent versus monophasic T cell lines, whose adoptive transfer to susceptible animals may result in respective recurrent or monophasic uveitis, we proposed grouping annotations on a subcellular layered interactome framework to analyze the specific bioprocesses that are linked to the recurrence of T cell autoimmunity. That is, the subcellular layered interactome was established by the Cytoscape and Cerebral plugin based on differential expression, global interactome, and subcellular localization information. Then, the layered interactomes were grouping annotated by the ClueGO plugin based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. The analysis showed that significant bioprocesses with autophagy were orchestrated in the cytoplasmic layered interactome and that mTOR may have a regulatory role in it. Furthermore, by setting up recurrent and monophasic uveitis in Lewis rats, we confirmed by transmission electron microscopy that, in comparison to the monophasic disease, recurrent uveitis in vivo showed significantly increased autophagy activity and extended lymphocyte infiltration to the affected retina. In summary, our framework methodology is a useful tool to disclose specific bioprocesses and molecular targets that can be attributed to a certain disease. Our results indicated that targeted inhibition of autophagy pathways may perturb the recurrence of uveitis.
authors.affiliation: Department of Immunology, Harbin Medical University, Harbin, China; Infection and Immunity, Key Laboratory of Heilongjiang Province, Harbin, China; College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Xiuzhi
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Anesthesiology, the 2nd Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Jingbo
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, the 4th Affiliated Hospital of Harbin Medical University, Harbin, China.
authors.forename: Dejing
authors.initials: D
authors.lastname: Shi
authors.affiliation: Department of Immunology, Harbin Medical University, Harbin, China; Infection and Immunity, Key Laboratory of Heilongjiang Province, Harbin, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Immunology, Harbin Medical University, Harbin, China; Infection and Immunity, Key Laboratory of Heilongjiang Province, Harbin, China.
authors.forename: Yucui
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Immunology, Harbin Medical University, Harbin, China; Infection and Immunity, Key Laboratory of Heilongjiang Province, Harbin, China.
authors.forename: Huanyu
authors.initials: H
authors.lastname: Ju
authors.affiliation: Department of Immunology, Harbin Medical University, Harbin, China; Infection and Immunity, Key Laboratory of Heilongjiang Province, Harbin, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Yang
authors.affiliation: The Blood Center of Hei Long Jiang Province, Harbin, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Sun
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Immunology, Harbin Medical University, Harbin, China; Infection and Immunity, Key Laboratory of Heilongjiang Province, Harbin, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Ren
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics* / Q000276:immunology; D001343:Autophagy / Q000235:genetics*; D019295:Computational Biology; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D042541:Intracellular Space / Q000235:genetics / Q000378:metabolism; D058977:Molecular Sequence Annotation; D051381:Rats; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000648:ultrastructure; D014605:Uveitis / Q000235:genetics* / Q000276:immunology