Abstract
ObjectiveTacrolimus (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. Lactobacillus acidophilus (LA) is reported to have therapeutic efficacy in immune-mediated diseases via T cell regulation.MethodsThis 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/lpr 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.ResultsMice 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/lpr 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 in vitro and in vivo. In vitro treatment with LA induced the production of indoleamine-2,3-dioxygenase, programmed death-ligand 1, and interleukin-10 via the specific intracellular adhesion molecule-3 grabbing non-integrin homolog-related 3 receptor signals.ConclusionThe present findings indicate that LA augments the therapeutic effect of Tac and modulates Th17/Treg balance in a murine model of SLE.
Highlights
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the presence of tissue-binding autoantibodies and the formation of immune complexes [1]
Mice presented with significant gut dysbiosis, which were subsequently recovered by the combination treatment of Tac and Lactobacillus acidophilus (LA)
The present findings indicate that LA augments the therapeutic effect of Tac and modulates T helper 17 (Th17)/Treg balance in a murine model of SLE
Summary
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the presence of tissue-binding autoantibodies and the formation of immune complexes [1]. Reduction in Treg cell production can cause an imbalance in T helper 17 (Th17) and Treg cell numbers, leading to dysfunctions in immune regulation; an imbalanced Th17/Treg ratio has been suggested as a pathognomonic immune alteration of SLE [9]. For these reasons, the therapeutic role and efficacy of Tac can be limited in SLE
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