Progranulin: A key player in autoimmune diseases

Cytokine. 2018 Jan:101:48-55. doi: 10.1016/j.cyto.2016.08.007. Epub 2016 Aug 12.

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 Treg differentiation 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.

Keywords: Autoimmune diseases; Progranulin; TNF; TNFR.

Publication types

  • Review

MeSH terms

  • Animals
  • Arthritis / immunology
  • Arthritis / physiopathology
  • Arthritis / therapy
  • Autoimmune Diseases / complications
  • Autoimmune Diseases / immunology*
  • Autoimmune Diseases / physiopathology*
  • Autoimmune Diseases / therapy
  • Humans
  • Inflammation / immunology
  • Inflammation / therapy
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / physiopathology
  • Inflammatory Bowel Diseases / therapy
  • Intercellular Signaling Peptides and Proteins / immunology*
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Intercellular Signaling Peptides and Proteins / therapeutic use
  • Interleukin-10 / genetics
  • Interleukin-10 / immunology
  • Macrophages / immunology
  • Mice
  • Osteoarthritis / immunology
  • Osteoarthritis / physiopathology
  • Osteoarthritis / therapy
  • Progranulins
  • Protein Binding
  • Psoriasis / immunology
  • Psoriasis / physiopathology
  • Psoriasis / therapy
  • Receptors, Tumor Necrosis Factor / immunology
  • Receptors, Tumor Necrosis Factor / metabolism
  • Signal Transduction / immunology
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / physiology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • GRN protein, human
  • Intercellular Signaling Peptides and Proteins
  • Progranulins
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Interleukin-10