DEL-1-Regulated Immune Plasticity and Inflammatory Disorders

Trends Mol Med. 2019 May;25(5):444-459. doi: 10.1016/j.molmed.2019.02.010. Epub 2019 Mar 15.

Abstract

In contrast to traditional immune cell-centered viewpoints, recent studies suggest that tissues are not passive recipients of immunity but have a 'regulatory say' over the host inflammatory response. Identification of tissue-derived homeostatic molecules regulating immune plasticity is seminal for understanding the inherent regulatory potential of different organs in the immune response. DEL-1 (developmental endothelial locus-1) is a secreted multidomain protein interacting with integrins and phospholipids and regulates, depending on its expression location, distinct stages of the host inflammatory response (from myelopoiesis over leukocyte recruitment to efferocytosis and resolution of inflammation). Here we synthesize recent evidence of DEL-1 as an exemplar local regulatory factor in the context of tissue immune plasticity and inflammatory disorders (such as periodontitis, multiple sclerosis, and pulmonary disorders), and discuss its potential as a therapeutic agent.

Keywords: DEL-1; EDIL3; homeostasis; inflammation; integrins; myelopoiesis; periodontitis; resolution.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Calcium-Binding Proteins / chemistry
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Cell Adhesion Molecules / chemistry
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Plasticity / immunology*
  • Chemotaxis, Leukocyte / genetics
  • Chemotaxis, Leukocyte / immunology
  • Disease Susceptibility
  • Homeostasis*
  • Humans
  • Immunomodulation*
  • Inflammation / etiology*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / therapy
  • Myelopoiesis / genetics
  • Myelopoiesis / immunology
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Organ Specificity
  • Phagocytosis
  • Protein Binding
  • Signal Transduction
  • Structure-Activity Relationship

Substances

  • Calcium-Binding Proteins
  • Cell Adhesion Molecules
  • EDIL3 protein, human