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  • br Mass spectrometry based technologies Oxysterols

    2020-05-21


    Mass spectrometry-based technologies Oxysterols tend not to be observed in global lipidomic analysis, whether shot-gun based electrospray ionisation – mass spectrometry (ESI-MS) or liquid chromatography (LC)-MS based. This is because of their comparatively low-abundance and poor ionisation characteristics. However, methods have been developed for shot-gun ESI – tandem MS (MS/MS) [23] and LC-MS/MS analysis [21,22]. Gas chromatography (GC)-MS also provides an excellent method for oxysterol and sterol analysis [24], but is less favoured in lipidomics laboratories.
    Lipidomics and oxysterol biochemistry
    Acknowledgement This work was supported by the UK Biotechnology and Biological Sciences Research Council (BBSRC, grant numbers BB/I001735/1 and BB/N015932/1 to WJG, BB/L001942/1 to YW).
    It is now widely accepted that oxysterols are more than metabolic intermediates but are actually lipid mediators. To qualify as a lipid mediator, a lipid BMH-21 should meet three conditions. First to be endogenous, second to have its levels altered depending on the physiological or pathological situation, and third to induce a signaling response when its levels are altered. As is evident from the papers published in this , oxysterols largely qualify as lipid mediators. First, they are endogenously produced, for the most part from cholesterol, via enzymatic reactions or following oxidation by reactive oxygen species. Second, the number of situations where altered oxysterol levels have been reported is continuing to increase. Such alterations have been described in situations as diverse as diseases of the cardiovascular system, central nervous system, eyes, the metabolic syndrome or cancer. Third, oxysterols can induce signaling responses either by altering cell membrane properties or by binding and activating several receptors. Any web-based literature search shows how the field is rapidly expanding. This is, not in small part, due to the “ENOR initiative” launched by Dr Iuliano and Dr Lizard in 2010 (). The European Network for Oxysterol Research (ENOR), via regular meetings and symposia, has helped moving the field forward by facilitating discussions and collaborations. In September 2017, we held in Brussels the seventh ENOR symposium entitled “Oxysterols and sterol derivatives in health and disease”. As for the previous meetings, this seventh edition was rich in high-level talks and intense scientific discussions. This special issue of “Biochimie” entitled “” is intended to convey these interesting research topics to a larger community, via both original reviews and research papers.
    Introduction The production of neutralizing antibodies by long-lived plasma cells and memory B cells upon antigen re-exposure underpins the protection afforded by most successful vaccines (Plotkin, 2008). These outputs from the germinal center (GC) are critically dependent on sequential CD4+ T cell help provided to B cells at multiple sites including the interfollicular zone (Kerfoot et al., 2011), T-B border (Garside et al., 1998, Okada et al., 2005), and within GCs (Allen et al., 2007, MacLennan, 1994, Victora and Nussenzweig, 2012) to drive antibody affinity maturation and memory formation (Crotty, 2011). The term follicular B helper T cells (Tfh) was originally used to describe human CD4+ T cells that express the chemokine receptor CXCR5, localize to the secondary follicle of tonsils, and provide cognate help to B cells (Breitfeld et al., 2000, Schaerli et al., 2000). The importance of Tfh cells to human health is underscored by the recurrent bacterial infections that occur when they are defective, and the autoimmune pathologies that develop when they are in excess (Tangye et al., 2013). Rapid developments in the Tfh field in recent years has been facilitated by the use of cell surface molecules, such as CXCR5, PD-1, and ICOS (Haynes et al., 2007, Rasheed et al., 2006), as surrogate markers for tracking Tfh cells in human subjects and genetic mouse models. Unfortunately, these markers of CD4+ T cell activation are not unique to Tfh cells. For example, CXCR5 is upregulated by multiple CD4+ T cell lineages upon activation in vivo (Ansel et al., 1999, Schaerli et al., 2001). Nevertheless, the recognition that the transcriptional repressor Bcl-6 is absolutely required for Tfh cell development firmly established them as a distinct CD4+ T cell lineage (Chtanova et al., 2004, Johnston et al., 2009, Nurieva et al., 2009, Yu et al., 2009). However, Bcl-6 expression is also not Tfh cell-specific as it is upregulated in all dividing CD4+ T cells during their interactions with dendritic cells (DCs) (Baumjohann et al., 2011, Kitano et al., 2011). Taken together, these uncertainties make it difficult to conclusively track the origin and fate of Tfh cells in the primary and secondary antibody response.