The Aryl Hydrocarbon Receptor compensates the adverse impact of smoking on the experimental autoimmune encephalomyelitis
Author(s): ,
J. Berg
Affiliations:
Neurology
,
C. David
Affiliations:
Neurology
,
A. Duscha
Affiliations:
Neurology
,
M. Peters
Affiliations:
Experimental Pneumology, Ruhr-Universität Bochum, Bochum, Germany
,
R. Gold
Affiliations:
Neurology
A. Haghikia
Affiliations:
Neurology
ECTRIMS Online Library. Berg J. Oct 12, 2018; 228929; P1088
Johannes Berg
Johannes Berg
Contributions
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Abstract

Abstract: P1088

Type: Poster Sessions

Abstract Category: Pathology and pathogenesis of MS - Environmental factors

Introduction: Among the differential environmental factors affecting the pathology of Multiple Sclerosis (MS), cigarette smoking is associated with a high risk on prevalence and progression. While respiratory and tumour-associated consequences of smoking are thoroughly investigated, its impact on the immune system is less well understood.
Aims: Here, we set out to investigate the role of the Aryl Hydrocarbon Receptor (AhR) - a highly conserved sensor for environmental chemicals - in a cigarette smoke-affected experimental autoimmune encephalomyelitis (EAE). Our previous experiments indicate the AhR to be an integral component in the antioxidant defence and the regulation of immune alterations evoked by smoking.
Methods: MOG35-55 EAE was induced in 8-week old AhR knockouts (AhRKO) and their wild type (WT) littermates. Beginning from the day of immunization, mice were restrained in an allay restraint and mounted to a nose-only inhalation tower (Data Sciences International) where they daily inhaled the smoke of four research grade cigarettes. Control mice were equally restrained to inhale room air. Spleen, lymph nodes and lungs were harvested at day 10 (priming), day 17 (peak of disease) and day 27 (remission) for flow cytometric analyses.
Results: In our experiments smoke inhalation did not affect the EAE disease course of WT animals, whereas AhRKO displayed a significant aggravation of symptoms. In the pre-clinical phase of EAE, inhalation of cigarette smoke resulted in reduced levels of B cells in all analysed organs and regulatory T cells in lymph nodes. NK cell abundance was decreased in the spleen and increased in lymph nodes. Compared to the stable levels in WT, smoke inhalation elevated splenic dendritic cells in the AhRKO. Moreover, the impact of smoke inhalation on B cells, NK cells and lymph node T cells was absent in these animals.
Conclusions: Our findings identify the AhR as an integral regulator of the cigarette smoke-modulated immune response in EAE. The recent results associate the AhR-mediated decrease of B cells and NK cells, as well as the stabilization of dendritic cells in the priming phase to counteract the exacerbation of disease symptoms, which was observed in smoke-afflicted AhRKO. Additional experiments will reveal if these AhR-regulated cell types display functional changes and if this impact persists over the whole disease course to further elaborate the immunomodulating aspects of AhR activation in the context of smoking and MS.
Disclosure: Johannes Berg: Nothing to disclose
Christina David: Nothing to disclose
Alexander Duscha: Nothing to disclose
Marcus Peters: Nothing to disclose
Ralf Gold serves on scientific advisory boards for Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, and Novartis; has received speaker honoraria from Biogen Idec, Teva Pharmaceutical Industries Ltd., Bayer Schering Pharma, and Novartis; serves as editor for Therapeutic Advances in Neurological Diseases and on the editorial boards of Experimental Neurology and the Journal of Neuroimmunology; and receives research support from Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, Genzyme, Merck Serono, and Novartis.
Aiden Haghikia received travel grants from Bayer Healthcare and Genzyme; has received speaker honoraria from Biogen Idec and limited research grants from Genzyme.

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