AUTHOR=Hamade Hussein , Stamps Jasmine T. , Stamps Dalton T. , More Shyam K. , Thomas Lisa S. , Blackwood Anna Y. , Lahcene Nawele L. , Castanon Sofi L. , Salumbides Brenda C. , Shimodaira Yosuke , Goodridge Helen S. , Targan Stephan R. , Michelsen Kathrin S. 

TITLE=BATF3 Protects Against Metabolic Syndrome and Maintains Intestinal Epithelial Homeostasis

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.841065

DOI=10.3389/fimmu.2022.841065

ISSN=1664-3224

ABSTRACT=<p>The intestinal immune system and microbiota are emerging as important contributors to the development of metabolic syndrome, but the role of intestinal dendritic cells (DCs) in this context is incompletely understood. BATF3 is a transcription factor essential in the development of mucosal conventional DCs type 1 (cDC1). We show that <italic>Batf3<sup>-/-</sup></italic> mice developed metabolic syndrome and have altered localization of tight junction proteins in intestinal epithelial cells leading to increased intestinal permeability. Treatment with the glycolysis inhibitor 2-deoxy-D-glucose reduced intestinal inflammation and restored barrier function in obese <italic>Batf3<sup>-/-</sup></italic> mice. High-fat diet further enhanced the metabolic phenotype and susceptibility to dextran sulfate sodium colitis in <italic>Batf3<sup>-/-</sup></italic> mice. Antibiotic treatment of <italic>Batf3<sup>-/-</sup></italic> mice prevented metabolic syndrome and impaired intestinal barrier function. <italic>Batf3<sup>-/-</sup></italic> mice have altered IgA-coating of fecal bacteria and displayed microbial dysbiosis marked by decreased obesity protective <italic>Akkermansia muciniphila</italic>, and <italic>Bifidobacterium</italic>. Thus, BATF3 protects against metabolic syndrome and preserves intestinal epithelial barrier by maintaining beneficial microbiota.</p>