Th17 Cells Are Activated in the Gut of Patients With MS

LONDON—Data suggest a selective activation of Th17 cells in the intestinal mucosa of patients with multiple sclerosis (MS), according to research presented at the 32nd Congress of the European Committee for Treatment and Research in MS (ECTRIMS). The findings validate previous reports in preclinical models of MS and provide the first evidence that gut immunity modulates MS pathogenesis in humans, according to the authors.

Animal models of MS have provided evidence that gut immunity and immune regulation are instrumental to maintaining immune tolerance towards the body’s own tissues. Immune regulation also helps to avoid inflammatory conditions in the intestine and at distal sites, thus helping to prevent organ-specific autoimmune diseases such as MS. Investigators hypothesize that by altering gut immunity, environmental factors acting at the intestinal level (eg, diet and microbiota modifications) increase the risk of developing autoimmune diseases such as MS in genetically at-risk individuals. Gloria Dalla Costa, MD, neurology resident at San Raffaele Hospital in Milan, and colleagues conducted a study to assess the potential role of gut immunity and microbiota modifications in MS pathogenesis.

The investigators analyzed gut immune cell subsets in intestinal mucosal samples isolated from 23 patients with relapsing-remitting MS and 16 age- and sex-matched healthy controls. Participants underwent esophago-gastro-duodenal endoscopy (EGDS) for diagnostic purposes. All patients with MS had not received corticosteroid treatments in the six months before EGDS, and had not received antibiotic treatment four weeks before EGDS. Patients with MS were receiving treatment with various disease-modifying drugs.

Dr. Dalla Costa and colleagues performed a multiparametric fluorescence-activated cell sorting analysis and measured the relative percentages of different T helper and Treg cell subsets in the small intestinal mucosa and peripheral blood. In the same patients with MS and healthy controls, the researchers performed a 16S metagenomic analysis of microbiota composition to correlate the activation of Th17 cells to a specific microbiota profile.

The investigators found that effector Th17 cells that play a crucial role in the pathogenesis of MS were present in the intestinal mucosa, but not in peripheral blood. Th22 cells were also detected only in the intestinal mucosa. In addition, patients with MS showed an increased percentage of activated Th17 cells (eg, IL-17, IL-22, and T cells) in the intestinal mucosa, with an increased Th17:FoxP3+Treg cell ratio, compared with healthy controls. This finding indicated activation of effector Th17 cells in the gut mucosa.

“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,” said Dr. Dalla Costa.

LONDON—Data suggest a selective activation of Th17 cells in the intestinal mucosa of patients with multiple sclerosis (MS), according to research presented at the 32nd Congress of the European Committee for Treatment and Research in MS (ECTRIMS). The findings validate previous reports in preclinical models of MS and provide the first evidence that gut immunity modulates MS pathogenesis in humans, according to the authors.

Animal models of MS have provided evidence that gut immunity and immune regulation are instrumental to maintaining immune tolerance towards the body’s own tissues. Immune regulation also helps to avoid inflammatory conditions in the intestine and at distal sites, thus helping to prevent organ-specific autoimmune diseases such as MS. Investigators hypothesize that by altering gut immunity, environmental factors acting at the intestinal level (eg, diet and microbiota modifications) increase the risk of developing autoimmune diseases such as MS in genetically at-risk individuals. Gloria Dalla Costa, MD, neurology resident at San Raffaele Hospital in Milan, and colleagues conducted a study to assess the potential role of gut immunity and microbiota modifications in MS pathogenesis.

The investigators analyzed gut immune cell subsets in intestinal mucosal samples isolated from 23 patients with relapsing-remitting MS and 16 age- and sex-matched healthy controls. Participants underwent esophago-gastro-duodenal endoscopy (EGDS) for diagnostic purposes. All patients with MS had not received corticosteroid treatments in the six months before EGDS, and had not received antibiotic treatment four weeks before EGDS. Patients with MS were receiving treatment with various disease-modifying drugs.

Dr. Dalla Costa and colleagues performed a multiparametric fluorescence-activated cell sorting analysis and measured the relative percentages of different T helper and Treg cell subsets in the small intestinal mucosa and peripheral blood. In the same patients with MS and healthy controls, the researchers performed a 16S metagenomic analysis of microbiota composition to correlate the activation of Th17 cells to a specific microbiota profile.

The investigators found that effector Th17 cells that play a crucial role in the pathogenesis of MS were present in the intestinal mucosa, but not in peripheral blood. Th22 cells were also detected only in the intestinal mucosa. In addition, patients with MS showed an increased percentage of activated Th17 cells (eg, IL-17, IL-22, and T cells) in the intestinal mucosa, with an increased Th17:FoxP3+Treg cell ratio, compared with healthy controls. This finding indicated activation of effector Th17 cells in the gut mucosa.

“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,” said Dr. Dalla Costa.

LONDON—Data suggest a selective activation of Th17 cells in the intestinal mucosa of patients with multiple sclerosis (MS), according to research presented at the 32nd Congress of the European Committee for Treatment and Research in MS (ECTRIMS). The findings validate previous reports in preclinical models of MS and provide the first evidence that gut immunity modulates MS pathogenesis in humans, according to the authors.

Animal models of MS have provided evidence that gut immunity and immune regulation are instrumental to maintaining immune tolerance towards the body’s own tissues. Immune regulation also helps to avoid inflammatory conditions in the intestine and at distal sites, thus helping to prevent organ-specific autoimmune diseases such as MS. Investigators hypothesize that by altering gut immunity, environmental factors acting at the intestinal level (eg, diet and microbiota modifications) increase the risk of developing autoimmune diseases such as MS in genetically at-risk individuals. Gloria Dalla Costa, MD, neurology resident at San Raffaele Hospital in Milan, and colleagues conducted a study to assess the potential role of gut immunity and microbiota modifications in MS pathogenesis.

The investigators analyzed gut immune cell subsets in intestinal mucosal samples isolated from 23 patients with relapsing-remitting MS and 16 age- and sex-matched healthy controls. Participants underwent esophago-gastro-duodenal endoscopy (EGDS) for diagnostic purposes. All patients with MS had not received corticosteroid treatments in the six months before EGDS, and had not received antibiotic treatment four weeks before EGDS. Patients with MS were receiving treatment with various disease-modifying drugs.

Dr. Dalla Costa and colleagues performed a multiparametric fluorescence-activated cell sorting analysis and measured the relative percentages of different T helper and Treg cell subsets in the small intestinal mucosa and peripheral blood. In the same patients with MS and healthy controls, the researchers performed a 16S metagenomic analysis of microbiota composition to correlate the activation of Th17 cells to a specific microbiota profile.

The investigators found that effector Th17 cells that play a crucial role in the pathogenesis of MS were present in the intestinal mucosa, but not in peripheral blood. Th22 cells were also detected only in the intestinal mucosa. In addition, patients with MS showed an increased percentage of activated Th17 cells (eg, IL-17, IL-22, and T cells) in the intestinal mucosa, with an increased Th17:FoxP3+Treg cell ratio, compared with healthy controls. This finding indicated activation of effector Th17 cells in the gut mucosa.

“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,” said Dr. Dalla Costa.