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Title

CCR 5 deficiency impairs CD 4+ T‐cell memory responses and antigenic sensitivity through increased ceramide synthesis

AuthorsMartín‐Leal, Ana; Blanco, Raquel; Casas, Josefina ; Sáez, María E.; Rodríguez‐Bovolenta, Elena; de Rojas, Itziar; Drechsler, Carina; Real, Luis Miguel; Fabriàs, Gemma ; Ruíz, Agustín; Castro, Mario; Schame, Wolfgang WA; Alarcón, Balbino ; Van Santen, Hisse M; Mañes, Santos
KeywordsCCR 5
HIV ‐1 infection
Ceramide synthesis
Issue Date11-Jun-2020
PublisherEMBO Press
CitationEMBO Journal e104749 (2020)
AbstractCCR 5 is not only a coreceptor for HIV ‐1 infection in CD 4+ T cells, but also contributes to their functional fitness. Here, we show that by limiting transcription of specific ceramide synthases, CCR 5 signaling reduces ceramide levels and thereby increases T‐cell antigen receptor (TCR ) nanoclustering in antigen‐experienced mouse and human CD 4+ T cells. This activity is CCR 5‐specific and independent of CCR 5 co‐stimulatory activity. CCR 5‐deficient mice showed reduced production of high‐affinity class‐switched antibodies, but only after antigen rechallenge, which implies an impaired memory CD 4+ T‐cell response. This study identifies a CCR 5 function in the generation of CD 4+ T‐cell memory responses and establishes an antigen‐independent mechanism that regulates TCR nanoclustering by altering specific lipid species.
Publisher version (URL)https://doi.org/10.15252/embj.2020104749
URIhttp://hdl.handle.net/10261/214168
DOIhttp://dx.doi.org/10.15252/embj.2020104749
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