AUTHOR=Kim Da Som , Park Youngjae , Choi Jeong-Won , Park Sung-Hwan , Cho Mi-La , Kwok Seung-Ki 

TITLE=Lactobacillus acidophilus Supplementation Exerts a Synergistic Effect on Tacrolimus Efficacy by Modulating Th17/Treg Balance in Lupus-Prone Mice via the SIGNR3 Pathway

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.696074

DOI=10.3389/fimmu.2021.696074

ISSN=1664-3224

ABSTRACT=<sec><title>Objective</title><p>Tacrolimus (Tac) is an immunosuppressant used in the treatment of systemic lupus erythematosus (SLE); however, it induces T cell subset imbalances by reducing regulatory T (Treg) cells. <italic>Lactobacillus acidophilus</italic> (LA) is reported to have therapeutic efficacy in immune-mediated diseases <italic>via</italic> T cell regulation.</p></sec><sec><title>Methods</title><p>This study investigated whether a combination therapy of LA and Tac improves the therapeutic efficacy of Tac by modulating T cell subset populations in an animal model of SLE. Eight-week-old MRL/<italic>lpr</italic> mice were orally administered with 5 mg/kg of Tac and/or 50 mg/kg of LA daily for 8 weeks. Cecal microbiota compositions, serum autoantibodies levels, the degree of proteinuria, histological changes in the kidney, and populations of various T cell subsets in the spleen were analyzed.</p></sec><sec><title>Results</title><p>Mice presented with significant gut dysbiosis, which were subsequently recovered by the combination treatment of Tac and LA. Double negative T cells in the peripheral blood and spleens of MRL/<italic>lpr</italic> mice were significantly decreased by the combination therapy. The combination treatment reduced serum levels of anti-dsDNA antibodies and Immunoglobulin G2a, and renal pathology scores were also markedly alleviated. The combination therapy induced Treg cells and decreased T helper 17 (Th17) cells both <italic>in vitro</italic> and <italic>in vivo</italic>. <italic>In vitro</italic> treatment with LA induced the production of indoleamine-2,3-dioxygenase, programmed death-ligand 1, and interleukin-10 <italic>via</italic> the specific intracellular adhesion molecule-3 grabbing non-integrin homolog-related 3 receptor signals.</p></sec><sec><title>Conclusion</title><p>The present findings indicate that LA augments the therapeutic effect of Tac and modulates Th17/Treg balance in a murine model of SLE.</p></sec>