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Antigen-specific activation of gut immune cells drives autoimmune neuroinflammation.

Gut microbes

Authors: Lena K Siewert, Kristina Berve, Elisabeth Pössnecker, Julia Dyckow, Amel Zulji, Ryan Baumann, Aida Munoz-Blazquez, Gurumoorthy Krishnamoorthy, David Schreiner, Sharon Sagan, Charlotte Nelson, Joseph J Sabatino, Kazuki Nagashima, Médéric Diard, Andrew J Macpherson, Stephanie C Ganal-Vonarburg, Michael A Fischbach, Scott S Zamvil, Lucas Schirmer, Sergio E Baranzini, Anne-Katrin Pröbstel

Microbiome-based therapies are promising new treatment avenues. While global alterations in microbiota composition have been shown in multiple sclerosis, whether and how gut microbiota influence autoimmune responses in an antigen-specific manner is unclear. Here, we genetically engineered gut bacteria to express a brain antigen and dissect their pathogenic potential in a murine model of autoimmune neuroinflammation. Colonization with bacteria expressing myelin - but not ovalbumin-peptide exacerbates an encephalitogenic immune response in the gut by activating antigen-specific T cells as well as B cells leading to accelerated neuroinflammatory disease. These results demonstrate how antigen-specific microbial modulation can influence autoimmunity, providing insight for development of therapeutic strategies targeting specific bacterial taxa for treatment of MS and other autoimmune diseases.

PMID: 41437842

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