Thymic stromal lymphopoietin induces adipose loss through sebum hypersecretion

Science. 2021 Jul 30;373(6554):eabd2893. doi: 10.1126/science.abd2893.

Abstract

Emerging studies indicate that the immune system can regulate systemic metabolism. Here, we show that thymic stromal lymphopoietin (TSLP) stimulates T cells to induce selective white adipose loss, which protects against obesity, improves glucose metabolism, and mitigates nonalcoholic steatohepatitis. Unexpectedly, adipose loss was not caused by alterations in food intake, absorption, or energy expenditure. Rather, it was induced by the excessive loss of lipids through the skin as sebum. TSLP and T cells regulated sebum release and sebum-associated antimicrobial peptide expression in the steady state. In human skin, TSLP expression correlated directly with sebum-associated gene expression. Thus, we establish a paradigm in which adipose loss can be achieved by means of sebum hypersecretion and uncover a role for adaptive immunity in skin barrier function through sebum secretion.

Publication types

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

MeSH terms

  • Adaptive Immunity
  • Adipose Tissue, White / anatomy & histology*
  • Animals
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Diet
  • Glucose / metabolism
  • Homeostasis
  • Humans
  • Immunoglobulins / metabolism
  • Lipid Metabolism
  • Mice
  • Non-alcoholic Fatty Liver Disease / prevention & control
  • Obesity / prevention & control
  • Pore Forming Cytotoxic Proteins / metabolism
  • Receptors, Cytokine / metabolism
  • Sebaceous Glands / metabolism
  • Sebum / metabolism*
  • Signal Transduction
  • Skin / immunology
  • Skin / metabolism*
  • T-Lymphocytes / physiology
  • Weight Loss

Substances

  • Cytokines
  • Immunoglobulins
  • Pore Forming Cytotoxic Proteins
  • Receptors, Cytokine
  • Tslpr protein, mouse
  • thymic stromal lymphopoietin
  • Glucose