title: Progranulin: A key player in autoimmune diseases.
abstract: Autoimmune disease encompasses an array of conditions with a variety of presentations and the involvement of multiple organs. Though the etiologies of many autoimmune conditions are unclear, uncontrolled inflammatory immune response is believed to be a major cause of disease development and progression. Progranulin (PGRN), an anti-inflammatory molecule with therapeutic effect in inflammatory arthritis, was identified as an endogenous antagonist of TNFα by competitively binding to TNFR. PGRN exerts its anti-inflammatory activity through multiple pathways, including induction of Tregdifferentiation and IL-10 expression and inhibition of chemokine release from macrophages. In addition, the protective role of PGRN has also been demonstrated in osteoarthritis, inflammatory bowel disease, and psoriasis. Intriguingly, PGRN was reported to contribute to development of insulin resistance in high-fat diet induced diabetes. Emerging evidences indicate that PGRN may also be associated with various autoimmune diseases, including systemic lupus erythematous, systemic sclerosis, multiple sclerosis and Sjogren's syndrome. This review summarizes recent studies of PGRN as a novel target molecule in the field of autoimmune disease, and provides updated information to inspire future studies.
authors.affiliation: Department of Orthopedics Surgery, New York University School of Medicine, New York, NY 10003, United States.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Jian
authors.affiliation: Department of Orthopedics Surgery, New York University School of Medicine, New York, NY 10003, United States; Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215004, China.
authors.forename: Guangfei
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Orthopedics Surgery, New York University School of Medicine, New York, NY 10003, United States.
authors.forename: Aubryanna
authors.initials: A
authors.lastname: Hettinghouse
authors.affiliation: Department of Orthopedics Surgery, New York University School of Medicine, New York, NY 10003, United States; Department of Cell Biology, New York University School of Medicine, New York, NY 10016, United States. Electronic address: chuanju.liu@nyumc.org.
authors.forename: Chuanju
authors.initials: C
authors.lastname: Liu
mesh_terms: D000818:Animals; D001168:Arthritis / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D001327:Autoimmune Diseases / Q000150:complications / Q000276:immunology* / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000628:therapy; D015212:Inflammatory Bowel Diseases / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D036341:Intercellular Signaling Peptides and Proteins / Q000276:immunology* / Q000378:metabolism / Q000627:therapeutic use; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D010003:Osteoarthritis / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D000077153:Progranulins; D011485:Protein Binding; D011565:Psoriasis / Q000276:immunology / Q000503:physiopathology / Q000628:therapy; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: C492314:GRN protein, human; D036341:Intercellular Signaling Peptides and Proteins; D000077153:Progranulins; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
keywords: Autoimmune diseases; Progranulin; TNF; TNFR