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Nat Rev Immunol. 2016 Mar;16(3):149-63. doi: 10.1038/nri.2015.18. Epub 2016 Feb 15.

Harnessing the plasticity of CD4(+) T cells to treat immune-mediated disease.

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Diabetes Center and Department of Medicine, University of California, San Francisco, San Francisco, California 94143, USA.


CD4(+) T cells differentiate and acquire distinct functions to combat specific pathogens but can also adapt their functions in response to changing circumstances. Although this phenotypic plasticity can be potentially deleterious, driving immune pathology, it also provides important benefits that have led to its evolutionary preservation. Here, we review CD4(+) T cell plasticity by examining the molecular mechanisms that regulate it - from the extracellular cues that initiate and drive cells towards varying phenotypes, to the cytosolic signalling cascades that decipher these cues and transmit them into the cell and to the nucleus, where these signals imprint specific gene expression programmes. By understanding how this functional flexibility is achieved, we may open doors to new therapeutic approaches that harness this property of T cells.

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