| First Author | Martín-Leal A | Year | 2020 |
| Journal | EMBO J | Volume | 39 |
| Issue | 15 | Pages | e104749 |
| PubMed ID | 32525588 | Mgi Jnum | J:293955 |
| Mgi Id | MGI:6452539 | Doi | 10.15252/embj.2020104749 |
| Citation | Martin-Leal A, et al. (2020) CCR5 deficiency impairs CD4(+) T-cell memory responses and antigenic sensitivity through increased ceramide synthesis. EMBO J 39(15):e104749 |
| abstractText | 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. CCR5-deficient mice showed reduced production of high-affinity class-switched antibodies, but only after antigen rechallenge, which implies an impaired memory CD4(+) T-cell response. This study identifies a CCR5 function in the generation of CD4(+) T-cell memory responses and establishes an antigen-independent mechanism that regulates TCR nanoclustering by altering specific lipid species. |
