Contributions
Abstract: 73
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - Immunology
Introduction: Several lines of evidence in animal models of Multiple Sclerosis (MS) indicate that gut immunity and immune regulation are instrumental to maintain immune tolerance towards self-tissues and avoid inflammatory conditions not only in the intestine but also at distal sites. These immunomodulatory mechanisms seem to prevent organ-specific autoimmune diseases such as MS. A current hypothesis is that environmental factors acting at the intestinal level (diet, microbiota modifications, etc..) increase the risk of developing autoimmune diseases such as MS in genetically-at risk individuals by altering gut immunity. The aim of our study is to assess the potential role of gut immunity and microbiota modifications in MS pathogenesis.
Methods: We analyzed gut immune cell subsets in intestinal mucosal samples isolated from 23 Relapsing-Remitting MS patients and 16 age and sex-matched healthy controls who underwent esophago-gastro-duodenal endoscopy (EGDS) for diagnostic purposes. All MS patients had not received corticosteroid treatments in the six months and antibiotic treatment 4 weeks before the EGDS and were treated with different disease modifying drugs (DMDs). We performed a multiparametric FACS analysis and measured the relative percentages of different T helper and Treg cell subsets in the small intestinal mucosa and peripheral blood (PBMC). In the same MS patients and healthy controls we performed a 16S metagenomic analysis of microbiota composition to correlate activation of Th17 cells to a specific microbiota profile.
Results: We found that effector Th17 cells that play a crucial role in the pathogenesis of MS, are present in the intestinal mucosa but not in PBMC. Th22 cells were also detected only in the intestinal mucosa. Importantly, MS patients showed an increased percentage of activated Th17 cells (IL-17+IL-22+ T cells) in the intestinal mucosa with an increased Th17/FoxP3+Treg cell ratio compared to healthy controls, indicating activation of effector Th17 cells in their gut mucosa.
Conclusions: Our data suggest that there is a selective activation of Th17 cells in the intestinal mucosa of MS patients. These findings validate previous reports in pre-clinical models of MS and provide the first evidence that gut immunity modulate MS pathogenesis in humans. Our next goal is to determine how environmental factors such as diet can modulate MS pathogenesis through alterations of gut microbiota composition and intestinal immunity.
Disclosure: V.M. has received personal compensation for activities with Biogen, MerckSerono, Bayer Schering, TEVA and Sanofi as a speaker. G.C.has received compensation for consulting services and/or speaking activities from Bayer Schering, Serono, Merck Serono, Teva, Sanofi and Biogen. G.D.C, M.J.M, A.M., I.C., M.R., M.F. report no discosures.
Abstract: 73
Type: Oral
Abstract Category: Pathology and pathogenesis of MS - Immunology
Introduction: Several lines of evidence in animal models of Multiple Sclerosis (MS) indicate that gut immunity and immune regulation are instrumental to maintain immune tolerance towards self-tissues and avoid inflammatory conditions not only in the intestine but also at distal sites. These immunomodulatory mechanisms seem to prevent organ-specific autoimmune diseases such as MS. A current hypothesis is that environmental factors acting at the intestinal level (diet, microbiota modifications, etc..) increase the risk of developing autoimmune diseases such as MS in genetically-at risk individuals by altering gut immunity. The aim of our study is to assess the potential role of gut immunity and microbiota modifications in MS pathogenesis.
Methods: We analyzed gut immune cell subsets in intestinal mucosal samples isolated from 23 Relapsing-Remitting MS patients and 16 age and sex-matched healthy controls who underwent esophago-gastro-duodenal endoscopy (EGDS) for diagnostic purposes. All MS patients had not received corticosteroid treatments in the six months and antibiotic treatment 4 weeks before the EGDS and were treated with different disease modifying drugs (DMDs). We performed a multiparametric FACS analysis and measured the relative percentages of different T helper and Treg cell subsets in the small intestinal mucosa and peripheral blood (PBMC). In the same MS patients and healthy controls we performed a 16S metagenomic analysis of microbiota composition to correlate activation of Th17 cells to a specific microbiota profile.
Results: We found that effector Th17 cells that play a crucial role in the pathogenesis of MS, are present in the intestinal mucosa but not in PBMC. Th22 cells were also detected only in the intestinal mucosa. Importantly, MS patients showed an increased percentage of activated Th17 cells (IL-17+IL-22+ T cells) in the intestinal mucosa with an increased Th17/FoxP3+Treg cell ratio compared to healthy controls, indicating activation of effector Th17 cells in their gut mucosa.
Conclusions: Our data suggest that there is a selective activation of Th17 cells in the intestinal mucosa of MS patients. These findings validate previous reports in pre-clinical models of MS and provide the first evidence that gut immunity modulate MS pathogenesis in humans. Our next goal is to determine how environmental factors such as diet can modulate MS pathogenesis through alterations of gut microbiota composition and intestinal immunity.
Disclosure: V.M. has received personal compensation for activities with Biogen, MerckSerono, Bayer Schering, TEVA and Sanofi as a speaker. G.C.has received compensation for consulting services and/or speaking activities from Bayer Schering, Serono, Merck Serono, Teva, Sanofi and Biogen. G.D.C, M.J.M, A.M., I.C., M.R., M.F. report no discosures.