title: Autophagy in Dendritic Cells and B Cells Is Critical for the Inflammatory State of TLR7-Mediated Autoimmunity.
abstract: Individuals suffering from autoimmune disorders possess a hyperactive cellular phenotype where tolerance to self-antigens is lost. Autophagy has been implicated in both the induction and prevention of autoimmunity, and modulators of this cellular recycling process hold high potential for the treatment of autoimmune diseases. In this study, we determine the effects of a loss of autophagy in dendritic cells (DCs), as well as both B cells and DCs, in a TLR7-mediated model of autoimmunity, similar to systemic lupus erythematosus, where both cell types are critical for disease. Although a loss of DC autophagy slowed disease, the combined loss of autophagy in both cell types resulted in a lethal sepsis-like environment, which included tissue inflammation and hyperproduction of inflammasome-associated cytokines. Ablation of B cell signaling reversed this phenotype, indicating that activation of these cells is an essential step in disease induction. Thus, autophagy plays a dichotomous role in this model of disease.
authors.affiliation: Program in Genetics, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111.
authors.forename: Chi G
authors.initials: CG
authors.lastname: Weindel
authors.affiliation: Division of Laboratory Animal Medicine, Tufts University, Boston, MA 02111; and.
authors.forename: Lauren J
authors.initials: LJ
authors.lastname: Richey
authors.affiliation: Department of Integrative Physiology and Pathobiology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111.
authors.forename: Abhiruchi J
authors.initials: AJ
authors.lastname: Mehta
authors.affiliation: Department of Integrative Physiology and Pathobiology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111.
authors.forename: Mansi
authors.initials: M
authors.lastname: Shah
authors.affiliation: Program in Genetics, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111; Brigitte.huber@tufts.edu.|Department of Integrative Physiology and Pathobiology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02111.
authors.forename: Brigitte T
authors.identifier: 0000-0001-5090-791X
authors.initials: BT
authors.lastname: Huber
mesh_terms: D000818:Animals; D015551:Autoimmunity; D001343:Autophagy / Q000502:physiology*; D001402:B-Lymphocytes / Q000502:physiology*; D003713:Dendritic Cells / Q000502:physiology*; D007249:Inflammation / Q000209:etiology*; D020382:Interleukin-18 / Q000096:biosynthesis; D008180:Lupus Erythematosus, Systemic / Q000209:etiology; D000072281:Lymphadenopathy / Q000209:etiology; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D013163:Splenomegaly / Q000209:etiology; D051199:Toll-Like Receptor 7 / Q000502:physiology*
chemical_list: D020382:Interleukin-18; D008562:Membrane Glycoproteins; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7