Modulation of T cell immune functions by the prostaglandin E(2) - cAMP pathway in chronic inflammatory states

Br J Pharmacol. 2012 May;166(2):411-9. doi: 10.1111/j.1476-5381.2011.01800.x.

Abstract

Cyclic AMP is the intracellular second messenger for a variety of immunoregulatory inflammatory mediators such as prostaglandin E2, adenosine and histamine that signal to effector T cells from monocytes, macrophages and regulatory T cells. Protein kinase A (PKA) type I localizes to lipid rafts in effector T cells during T cell activation and directly modulates proximal signal events including phosphorylation of C-terminal Src kinase (Csk), which initiates a negative signal pathway that fine-tunes the T cell activation process. The PKA-Csk immunoregulatory pathway is scaffolded by the A kinase anchoring protein ezrin, the Csk binding protein phosphoprotein associated with glycosphingolipid-enriched membrane microdomains and the linker protein ezrin/radixin/moesin binding protein of 50 kDa. This pathway is hyperactivated in chronic infections with an inflammatory component such as HIV, other immunodeficiencies and around solid tumours as a consequence of local inflammation leading to inhibition of anti-tumour immunity. LINKED ARTICLES This article is part of a themed section on Novel cAMP Signalling Paradigms. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.166.issue-2.

Publication types

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

MeSH terms

  • Animals
  • Colorectal Neoplasms / immunology
  • Cyclic AMP / immunology*
  • Cyclic AMP-Dependent Protein Kinases / immunology
  • Cytoskeletal Proteins / immunology
  • Dinoprostone / immunology*
  • HIV Infections / immunology
  • Humans
  • Inflammation / immunology
  • T-Lymphocytes / immunology*

Substances

  • Cytoskeletal Proteins
  • ezrin
  • Cyclic AMP
  • Cyclic AMP-Dependent Protein Kinases
  • Dinoprostone