Constitutive activity of NF-kappa B in myeloid cells drives pathogenicity of monocytes and macrophages during autoimmune neuroinflammation

  • The NF-κB/REL-family of transcription factors plays a central role in coordinating the expression of a wide variety of genes controlling immune responses including autoimmunity of the central nervous system (CNS). The inactive form of NF-κB consists of a heterodimer which is complexed with its inhibitor, IκB. Conditional knockout-mice for IκBα in myeloid cells (lysMCreIκBαfl/fl) have been generated and are characterized by a constitutive activation of NF-κB proteins allowing the study of this transcription factor in myelin-oligodendrocyte-glycoprotein induced experimental autoimmune encephalomyelitis (MOG-EAE), a well established experimental model for autoimmune demyelination of the CNS. InThe NF-κB/REL-family of transcription factors plays a central role in coordinating the expression of a wide variety of genes controlling immune responses including autoimmunity of the central nervous system (CNS). The inactive form of NF-κB consists of a heterodimer which is complexed with its inhibitor, IκB. Conditional knockout-mice for IκBα in myeloid cells (lysMCreIκBαfl/fl) have been generated and are characterized by a constitutive activation of NF-κB proteins allowing the study of this transcription factor in myelin-oligodendrocyte-glycoprotein induced experimental autoimmune encephalomyelitis (MOG-EAE), a well established experimental model for autoimmune demyelination of the CNS. In comparison to controls, lysMCreIκBαfl/fl mice developed a more severe clinical course of EAE. Upon histological analysis on day 15 p.i., there was an over two fold increased infiltration of T-cells and macrophages/microglia. In addition, lysMCreIκBαfl/fl mice displayed an increased expression of the NF-κB dependent factor inducible nitric oxide synthase in inflamed lesions. These changes in the CNS are associated with increased numbers of CD11b positive splenocytes and a higher expression of Ly6c on monocytes in the periphery. Well in accordance with these changes in the myeloid cell compartment, there was an increased production of the monocyte cytokines interleukin(IL)-12 p70, IL-6 and IL-1beta in splenocytes. In contrast, production of the T-cell associated cytokines interferon gamma (IFN-gamma) and IL-17 was not influenced. In summary, myeloid cell derived NF-κB plays a crucial role in autoimmune inflammation of the CNS and drives a pathogenic role of monocytes and macrophages independently from T-cells.show moreshow less

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Metadaten
Author:Gisa Ellrichmann, Jan Thöne, De-Hyung Lee, Rudolph A. Rupec, Ralf Gold, Ralf A. Linker
URN:urn:nbn:de:bvb:29-opus-35743
Title of the journal / compilation:Journal of Neuroinflammation 9.15 (2012): 09.10.2012 <http://www.jneuroinflammation.com/content/9/1/15>
Document Type:Article
Language:English
Date of Publication (online):2012/10/09
Publishing Institution:Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU)
Release Date:2012/10/09
Tag:NF-kappaB; cytokines; experimental autoimmune encephalomyelitis; myeloid cells
SWD-Keyword:-
Original publication:Journal of Neuroinflammation 9.15 (2012): 09.10.2012 <http://www.jneuroinflammation.com/content/9/1/15>
Institutes:Medizinische Fakultät -ohne weitere Spezifikation-
Dewey Decimal Classification:610 Medizin und Gesundheit
Collections:Von der FAU geförderte Open Access Artikel 2012

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