Contributions
Abstract: 164
Type: Oral
The gut microbiome is of increasing interest as an immune mediated reservoir associated with a number of experimental neurologic conditions including CNS demyelinating disease. The gut microbiome is a complex organ within each of us comprised of trillions of microflora, the predominant being commensal bacteria. The pioneering explorations in our lab into the role of the gut microbiome in inflammatory CNS disease correlated the association of disease resistance and/or susceptibility to alterations in both the diversity and abundances of gut commensals in the experimental EAE model. Disease resistance is manifested via the induction of both T and B regulatory cells derived from the gut associated llymphoid tissue (GALT). whereas disease progression and inflammatory activity associated with the induction of IL-17 T cells. The reservoir for both regulatory and inflammatory populations is within the gut associated lymphoid tissue (GALT). As the gut microbiome is comprised of trillions of diverse bacteria we chose to utilize a reductive approach and investigated the ability of a single polysaccharide capsular antigen (PSA) derived from the human symbiont, B. fragilis to explore the capacity to induce immune regulation during CNS demyelination. This commensal derived molecule, the only single product yet identified from the microbiome, can induce immune regulation via the upregulation of IL-10 producing CD39+ T regs that can be adoptively transferred and protect against EAE. Similar observations are noted by PSA mediated induction of IL-10 producing GALT derived B regulatory cells. Studies using human PBMC demonstrate the capacity of PSA to induce phenotypically distinct CD39+, IL-10 producing Tregs as well as human B regs ex vivo . Upregulation of GALT derived protective IL-10 producing CD39+ T regs is found in EAE mice following treatment with several approved IMD therapies including glatiramer acetate, teriflunomide and anti-CD52. Enhancement of CD39+ T cells can be identified amongst the PBMC from MS patients following treatment with either fingolomid or anti-CD52 suggesting a common effect of currently available treatments for MS on the gut microbiome and GALT. A common denominator for most of the known risk factors for MS is the gut microbiome perhaps making it the most important environmental risk factor in this disease. Further explorations elucidating the role of the gut microbiome may reveal a 'treasure trove' of molecules and approaches for treating human MS.
Disclosure: Funding through the NIH, the National MS Society, Teva Neuroscience and Genzyme
Abstract: 164
Type: Oral
The gut microbiome is of increasing interest as an immune mediated reservoir associated with a number of experimental neurologic conditions including CNS demyelinating disease. The gut microbiome is a complex organ within each of us comprised of trillions of microflora, the predominant being commensal bacteria. The pioneering explorations in our lab into the role of the gut microbiome in inflammatory CNS disease correlated the association of disease resistance and/or susceptibility to alterations in both the diversity and abundances of gut commensals in the experimental EAE model. Disease resistance is manifested via the induction of both T and B regulatory cells derived from the gut associated llymphoid tissue (GALT). whereas disease progression and inflammatory activity associated with the induction of IL-17 T cells. The reservoir for both regulatory and inflammatory populations is within the gut associated lymphoid tissue (GALT). As the gut microbiome is comprised of trillions of diverse bacteria we chose to utilize a reductive approach and investigated the ability of a single polysaccharide capsular antigen (PSA) derived from the human symbiont, B. fragilis to explore the capacity to induce immune regulation during CNS demyelination. This commensal derived molecule, the only single product yet identified from the microbiome, can induce immune regulation via the upregulation of IL-10 producing CD39+ T regs that can be adoptively transferred and protect against EAE. Similar observations are noted by PSA mediated induction of IL-10 producing GALT derived B regulatory cells. Studies using human PBMC demonstrate the capacity of PSA to induce phenotypically distinct CD39+, IL-10 producing Tregs as well as human B regs ex vivo . Upregulation of GALT derived protective IL-10 producing CD39+ T regs is found in EAE mice following treatment with several approved IMD therapies including glatiramer acetate, teriflunomide and anti-CD52. Enhancement of CD39+ T cells can be identified amongst the PBMC from MS patients following treatment with either fingolomid or anti-CD52 suggesting a common effect of currently available treatments for MS on the gut microbiome and GALT. A common denominator for most of the known risk factors for MS is the gut microbiome perhaps making it the most important environmental risk factor in this disease. Further explorations elucidating the role of the gut microbiome may reveal a 'treasure trove' of molecules and approaches for treating human MS.
Disclosure: Funding through the NIH, the National MS Society, Teva Neuroscience and Genzyme