Alpha-methylacyl-CoA racemase deletion has mutually counteracting effects on T-cell responses, associated with unchanged course of EAE

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• 作者：Nadja Tafferner ; Julia Barthelmes ; Max Eberle ; Thomas Ulshö ; fer ; Marina Henke ; Natasja deBruin ; Christoph A. Mayer ; Christian Foerch ; Gerd Geisslinger ; Michael J. Parnham and Susanne Schiffmann
• 关键词：Alpha-methylacyl-CoA racemase (AMACR) ; Cytokines ; EAE ; Multiple sclerosis ; T cells
• 刊名：European Journal of Immunology
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：46
• 期：3
• 页码：570-581
• 全文大小：937K
• ISSN：1521-4141

文摘

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Altering the metabolism of immune cells is an attractive strategy to modify their activity during autoimmunity in MS. We investigated the effect of modulating fatty acid metabolism in an animal model of MS, EAE. Alpha-methylacyl-CoA racemase (AMACR) converts R-configuration branched fatty acids into the S-configuration, thereby preparing them for β-oxidation. We observed a significant, disease-dependent elevation of AMACR expression in monocytes and T cells from blood, draining lymph nodes and spleen of EAE mice during the preclinical phase. In vitro analysis revealed that the proliferation of T cells was inhibited in AMACR KO mice, but T-cell polarization was switched toward a pathogenic state involving the production of more IFN- and IL-17, but less IL-4. These opposing effects appeared to cancel out each other in vivo, because AMACR KO EAE mice showed a marginal increase in the severity of early clinical symptoms. AMACR was not regulated in the white blood cells of MS patients. Our data show that AMACR is regulated in immune cells during EAE, but it is not a suitable target for the treatment of MS due to its opposing effects.