The Chemokine Receptor CCR5 Links Memory CD4 T Cell Metabolism to T Cell Antigen Receptor Nanoclustering.

The inhibition of anabolic pathways, such as aerobic glycolysis, is a metabolic cornerstone of memory T cell differentiation and function. However, the signals that hamper these anabolic pathways are not completely known. Recent evidence pinpoints the chemokine receptor CCR5 as an important player in CD4 T cell memory responses by regulating T cell antigen receptor (TCR) nanoclustering in an antigen-independent manner.

CCR5 deficiency impairs CD4 T-cell memory responses and antigenic sensitivity through increased ceramide synthesis.

CCR5 is not only a coreceptor for HIV-1 infection in CD4 T cells, but also contributes to their functional fitness. Here, we show that by limiting transcription of specific ceramide synthases, CCR5 signaling reduces ceramide levels and thereby increases T-cell antigen receptor (TCR) nanoclustering in antigen-experienced mouse and human CD4 T cells. This activity is CCR5-specific and independent of CCR5 co-stimulatory activity.

Chemokine Receptor Signaling and the Hallmarks of Cancer.

The chemokines are a family of chemotactic cytokines that mediate their activity by acting on seven-transmembrane-spanning G protein-coupled receptors. Both the ability of the chemokines and their receptors to form homo- and heterodimers and the promiscuity of the chemokine-chemokine receptor interaction endow this protein family with enormous signaling plasticity and complexity that are not fully understood at present. Chemokines were initially identified as essential regulators of homeostatic and inflammatory trafficking of innate and adaptive leucocytes from lymphoid organs to tissues.