Metabolic Pathways That Control Skin Homeostasis and Inflammation

Trends Mol Med. 2020 Nov;26(11):975-986. doi: 10.1016/j.molmed.2020.04.004. Epub 2020 May 1.

Abstract

Keratinocytes and skin immune cells are actively metabolizing nutrients present in their microenvironment. This is particularly important in common chronic inflammatory skin diseases such as psoriasis and atopic dermatitis, characterized by hyperproliferation of keratinocytes and expansion of inflammatory cells, thus suggesting increased cell nutritional requirements. Proliferating inflammatory cells and keratinocytes express high levels of glucose transporter (GLUT)1, l-type amino acid transporter (LAT)1, and cationic amino acid transporters (CATs). Main metabolic regulators such as hypoxia-inducible factor (HIF)-1α, MYC, and mechanistic target of rapamycin (mTOR) control immune cell activation, proliferation, and cytokine release. Here, we provide an updated perspective regarding the potential role of nutrient transporters and metabolic pathways that could be common to immune cells and keratinocytes, to control psoriasis and atopic dermatitis.

Keywords: amino acid; atopic dermatitis; glucose; metabolism; psoriasis; transporters.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acids / metabolism
  • Animals
  • Biological Transport
  • Dermatitis / etiology*
  • Dermatitis / metabolism*
  • Dermatitis / pathology
  • Disease Susceptibility*
  • Glucose / metabolism
  • Homeostasis*
  • Humans
  • Keratinocytes / metabolism
  • Keratinocytes / pathology
  • Membrane Transport Proteins / metabolism
  • Metabolic Networks and Pathways*
  • Signal Transduction
  • Skin / metabolism*
  • Skin Physiological Phenomena*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Amino Acids
  • Membrane Transport Proteins
  • TOR Serine-Threonine Kinases
  • Glucose