LIF in the regulation of T-cell fate and as a potential therapeutic
- PMID: 21368774
- DOI: 10.1038/gene.2011.9
LIF in the regulation of T-cell fate and as a potential therapeutic
Abstract
At the heart of lineage commitment within the adaptive immune response is the intrinsic genetic plasticity of the naive peripheral T lymphocyte (T cell). Primary activation by presentation of cognate antigen is coupled to rapid T-cell cycling and progressive epigenetic changes that guide the cell down distinct T-cell lineages, either effector (Th1, Th2, Th17) or tolerogenic (Treg). Fate choice is influenced both by strength of the priming activation signal and by cues from the micro-environment that are integrated with lineage-specific gene expression profiles, eventually becoming hard-wired in the fully differentiated cell. The micro-environmental cues include cytokines, and the discovery that leukaemia inhibitory factor (LIF) and interleukin (IL)-6 counter-regulate development of the Treg and Th17 lineages places LIF within the core regulatory circuitry of T cells. I first summarise current understanding of LIF and the LIF receptor in the context of T cells. Next, the central relevance of the LIF/IL-6 axis in immune-mediated disease is set in the context of (i) a new nano-therapeutic approach for targeted delivery of LIF and (ii) MARCH-7, a novel E3-ligase discovered to have a central mechanistic role in LIF-mediated T-cell biology, functioning as a rheostat-type regulator of endogenous LIF-signalling.
Comment in
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LIF and multiple sclerosis: One protein with two healing properties.Mult Scler Relat Disord. 2018 Feb;20:223-227. doi: 10.1016/j.msard.2018.01.018. Epub 2018 Jan 31. Mult Scler Relat Disord. 2018. PMID: 29448112 No abstract available.
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