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Myeloid 12/15-LOX regulates B cell numbers and innate immune antibody levels in vivo

Lauder, Sarah N., Tyrrell, Victoria J., Allen-Redpath, Keith, Aldrovandi, MacEler, Gray, David, Collins, Peter, Jones, Simon A., Taylor, Philip R. and O'Donnell, Valerie 2017. Myeloid 12/15-LOX regulates B cell numbers and innate immune antibody levels in vivo. Wellcome Open Research 2 (1) 10.12688/wellcomeopenres.10308.1

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Abstract

Background. The myeloid enzyme 12/15-lipoxygenase (LOX), which generates bioactive oxidized lipids, has been implicated in numerous inflammatory diseases, with several studies demonstrating an improvement in pathology in mice lacking the enzyme. However, the ability of 12/15-LOX to directly regulate B cell function has not been studied. Methods. The influence of 12/15-LOX on B cell phenotype and function, and IgM generation, was compared using wildtype (WT) and 12/15-LOX (Alox15-/-) deficient mice. The proliferative and functional capacity of splenic CD19+ B cells was measured in vitro in response to various toll-like receptor agonists. Results. WT and Alox15-/- displayed comparable responses. However in vivo, splenic B cell numbers were significantly elevated in Alox15-/- mice with a corresponding elevation in titres of total IgM in lung, gut and serum, and lower serum IgM directed against the 12/15-LOX product, 12-hydroxyeicosatetraenoic acid-phosphatidylethanolamine (HETE-PE). Discussion. Myeloid 12/15-LOX can regulate B cell numbers and innate immune antibody levels in vivo, potentially contributing to its ability to regulate inflammatory disease. Furthermore, the alterations seen in 12/15-LOX deficiency likely result from changes in the equilibrium of the immune system that develop from birth. Further studies in disease models are warranted to elucidate the contribution of 12/15-LOX mediated alterations in B cell numbers and innate immune antibody generation to driving inflammation in vivo.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Publisher: F1000Research
ISSN: 2398-502X
Funders: Wellcome Trust
Date of First Compliant Deposit: 12 May 2017
Date of Acceptance: 4 January 2017
Last Modified: 25 Feb 2019 00:23
URI: http://orca.cf.ac.uk/id/eprint/100487

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