CXCR4-CCR5: A couple modulating T cell functions

Rita Lucia Contento, Barbara Molon, Cedric Boularan, Tullio Pozzan, Santos Manes, Stefano Marullo, Antonella Viola

Research output: Contribution to journalArticlepeer-review

Abstract

Chemokines and their receptors direct leukocyte migration among blood, lymph and tissues. Evidence has recently accumulated that, besides their chemotactic functions, chemokine receptors are highly versatile players that fine tune immune responses. During human T cell activation by antigen-presenting cells, the chemokine receptors CCR5 and CXCR4 are recruited into the immunological synapse, where they deliver costimulatory signals. However, the molecular mechanisms allowing signaling versatility of chemokine receptors are unknown. Here, we describe the functional interaction between CXCR4 and CCR5 to exert specific biological functions and modulate T lymphocyte responses. We demonstrate that simultaneous expression and cooperation between CCR5 and CXCR4 are required for chemokine-induced T cell costimulation at the immunological synapse. In addition, we provide evidence for a physical association of the two receptors in a signaling complex that activates distinct T cell functions. We suggest that cooperation between receptors represents one key strategy for the functional plasticity of chemokines.

Original languageEnglish
Pages (from-to)10101-10106
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number29
DOIs
Publication statusPublished - Jul 22 2008

Keywords

  • Chemokine receptors
  • Heterodimerization
  • T cell costimulation

ASJC Scopus subject areas

  • General
  • Genetics

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