Mikael V Ringh1, Michael Hagemann-Jensen2, Maria Needhamsen1, Susanna Kullberg3, Jan Wahlström2, Johan Grunewald2, Boel Brynedal4, Maja Jagodic1, Tomas J Ekström1, Johan Öckinger2, Lara Kular1. 1. Department of Clinical Neuroscience and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. 2. Department of Medicine, Solna and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. 3. Department of Medicine, Solna and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden/Respiratory Medicine Division, Department of Medicine and Theme Inflammation and Infection, Karolinska University Hospital, Stockholm, Sweden. 4. Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Abstract
BACKGROUND: Despite compelling evidence that cigarette smoking impacts the risk of developing multiple sclerosis (MS), little is known about smoking-associated changes in the primary exposed lung cells of patients. OBJECTIVES: We aimed to examine molecular changes occurring in bronchoalveolar lavage (BAL) cells from MS patients in relation to smoking and in comparison to healthy controls (HCs). METHODS: We profiled DNA methylation in BAL cells from female MS (n = 17) and HC (n = 22) individuals, using Illumina Infinium EPIC and performed RNA-sequencing in non-smokers. RESULTS: The most prominent changes were found in relation to smoking, with 1376 CpG sites (adjusted P < 0.05) differing between MS smokers and non-smokers. Approximately 30% of the affected genes overlapped with smoking-associated changes in HC, leading to a strong common smoking signature in both MS and HC after gene ontology analysis. Smoking in MS patients resulted in additional discrete changes related to neuronal processes. Methylome and transcriptome analyses in non-smokers suggest that BAL cells from MS patients display very subtle (not reaching adjusted P < 0.05) but concordant changes in genes connected to reduced transcriptional/translational processes and enhanced cellular motility. CONCLUSIONS: Our study provides insights into the impact of smoking on lung inflammation and immunopathogenesis of MS.
BACKGROUND: Despite compelling evidence that cigarette smoking impacts the risk of developing multiple sclerosis (MS), little is known about smoking-associated changes in the primary exposed lung cells of patients. OBJECTIVES: We aimed to examine molecular changes occurring in bronchoalveolar lavage (BAL) cells from MS patients in relation to smoking and in comparison to healthy controls (HCs). METHODS: We profiled DNA methylation in BAL cells from female MS (n = 17) and HC (n = 22) individuals, using Illumina Infinium EPIC and performed RNA-sequencing in non-smokers. RESULTS: The most prominent changes were found in relation to smoking, with 1376 CpG sites (adjusted P < 0.05) differing between MS smokers and non-smokers. Approximately 30% of the affected genes overlapped with smoking-associated changes in HC, leading to a strong common smoking signature in both MS and HC after gene ontology analysis. Smoking in MS patients resulted in additional discrete changes related to neuronal processes. Methylome and transcriptome analyses in non-smokers suggest that BAL cells from MS patients display very subtle (not reaching adjusted P < 0.05) but concordant changes in genes connected to reduced transcriptional/translational processes and enhanced cellular motility. CONCLUSIONS: Our study provides insights into the impact of smoking on lung inflammation and immunopathogenesis of MS.
Entities:
Keywords:
DNA methylation; bronchoalveolar cells; epigenetics; immunopathogenesis; multiple sclerosis; smoking