Regulation of barrier immunity and homeostasis by integrin-mediated transforming growth factor β activation

Immunology. 2020 Jun;160(2):139-148. doi: 10.1111/imm.13162. Epub 2019 Dec 25.

Abstract

Transforming growth factor β (TGF-β) is a multifunctional cytokine that regulates cell growth, differentiation, adhesion, migration and death dependent on cell type, developmental stage, or tissue conditions. Various cell types secrete TGF-β, but always as an inactive complex. Hence, for TGF-β to function, this latent complex must somehow be activated. Work in recent years has highlighted a critical role for members of the αv integrin family, including αv β1 , αv β3 , αv β5 , αv β6 and αv β8 that are involved in TGF-β activation in various contexts, particularly at barrier sites such as the gut, lung and skin. The integrins facilitating this context- and location-specific regulation can be dysregulated in certain diseases, so are potential therapeutic targets in a number of disorders. In this review, we discuss the role of TGF-β at these barrier sites with a focus on how integrin-mediated TGF-β activation regulates tissue and immune homeostasis, and how this is altered in disease.

Keywords: immune system; integrins; intestine; lung; skin; transforming growth factor-β.

Publication types

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

MeSH terms

  • Animals
  • Disease Models, Animal
  • Gastrointestinal Microbiome / immunology
  • Homeostasis / immunology*
  • Humans
  • Integrin alphaV / metabolism*
  • Intestinal Diseases / immunology
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology
  • Lung / immunology
  • Lung / metabolism
  • Lung Diseases / immunology
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / metabolism
  • Signal Transduction / immunology*
  • Skin / immunology
  • Skin / metabolism
  • Skin / microbiology
  • Skin Diseases / immunology
  • Transforming Growth Factor beta / metabolism*

Substances

  • Integrin alphaV
  • Transforming Growth Factor beta