The Genetic Background of Mice Influences the Effects of Cigarette Smoke on Onset and Severity of Experimental Autoimmune Encephalomyelitis.

Abstract

Multiple sclerosis (MS) is the most common inflammatory disorder of the central nervous system (CNS) in young adults leading to severe disability. Besides genetic traits, environmental factors contribute to MS pathogenesis. Cigarette smoking increases the risk of MS in an HLA-dependent fashion, but the underlying mechanisms remain unknown. Here, we explored the effect of cigarette smoke exposure on spontaneous and induced models of experimental autoimmune encephalomyelitis (EAE) by evaluating clinical disease and, when relevant, blood leukocytes and histopathology. In the relapsing-remitting (RR) transgenic model in SJL/J mice, we observed very low incidence in both smoke-exposed and control groups. In the optico-spinal encephalomyelitis (OSE) double transgenic model in C57BL/6 mice, the early onset of EAE prevented a meaningful evaluation of the effects of cigarette smoke. In EAE models induced by immunization, daily exposure to cigarette smoke caused a delayed onset of EAE followed by a protracted disease course in SJL/J mice. In contrast, cigarette smoke exposure ameliorated the EAE clinical score in C57BL/6J mice. Our exploratory studies therefore show that genetic background influences the effects of cigarette smoke on autoimmune neuroinflammation. Importantly, our findings expose the challenge of identifying an animal model for studying the influence of cigarette smoke in MS.

• Authors: Gaby Enzmann, Roberto Adelfio, Aurélie Godel, Neda Haghayegh Jahromi, Silvia Tietz, Sabrina S Burgener, Urban Deutsch, Hartmut Wekerle, Charaf Benarafa, Britta Engelhardt
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 20 Issue 6 (Mar 21 2019) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 30901861 (Publication Type: Journal Article)

Topics

• Age of Onset
• Animals
• Biopsy
• Brain (metabolism, pathology)
• Disease Models, Animal
• Disease Susceptibility
• Encephalomyelitis, Autoimmune, Experimental (diagnosis, etiology, metabolism)
• Genetic Background
• Immunohistochemistry
• Mice
• Multiple Sclerosis (diagnosis, etiology, metabolism)
• Phenotype
• Risk Assessment
• Risk Factors
• Severity of Illness Index
• Smoking (adverse effects)
• Spinal Cord (metabolism, pathology)