The role of A Disintegrin and Metalloproteinase (ADAM)-10 in T helper cell biology

Biochim Biophys Acta Mol Cell Res. 2022 Apr;1869(4):119192. doi: 10.1016/j.bbamcr.2021.119192. Epub 2022 Jan 1.

Abstract

A Disintegrin and Metalloproteinases (ADAM)-10 is a member of a family of membrane-anchored proteinases that regulate a broad range of cellular functions with central roles within the immune system. This has spurred the interest to modulate ADAM activity therapeutically in immunological diseases. CD4 T helper (Th) cells are the key regulators of adaptive immune responses. Their development and function is strongly dependent on Notch, a key ADAM-10 substrate. However, Th cells rely on a variety of additional ADAM-10 substrates regulating their functional activity at multiple levels. The complexity of both, the ADAM substrate expression as well as the functional consequences of ADAM-mediated cleavage of the various substrates complicates the analysis of cell type specific effects. Here we provide an overview on the major ADAM-10 substrates relevant for CD4 T cell biology and discuss the potential effects of ADAM-mediated cleavage exemplified for a selection of important substrates.

Keywords: Adam10; CD154; CD25; CD4 T helper cells; Notch; T-cell biology.

Publication types

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

MeSH terms

  • ADAM10 Protein / metabolism*
  • ADAM17 Protein / metabolism
  • B7-H1 Antigen / metabolism
  • Cell Differentiation
  • Cell Proliferation
  • Humans
  • Receptors, Interleukin-2 / metabolism
  • Receptors, Notch / metabolism
  • Signal Transduction
  • T-Lymphocytes, Helper-Inducer / cytology
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / metabolism*

Substances

  • B7-H1 Antigen
  • Receptors, Interleukin-2
  • Receptors, Notch
  • ADAM10 Protein
  • ADAM17 Protein