10.6084/m9.figshare.12514370.v1 Jean N. Manirarora Jean N. Manirarora Michele M. Kosiewicz Michele M. Kosiewicz Pascale Alard Pascale Alard Feeding lactobacilli impacts lupus progression in (NZBxNZW)F1 lupus-prone mice by enhancing immunoregulation Taylor & Francis Group 2020 Lupus probiotic Treg IL-10 DC tolerance 2020-06-19 11:55:20 Journal contribution https://tandf.figshare.com/articles/journal_contribution/Feeding_lactobacilli_impacts_lupus_progression_in_NZBxNZW_F1_lupus-prone_mice_by_enhancing_immunoregulation/12514370 <p>Although the relationship between autoimmunity and microorganisms is complex, there is evidence that microorganisms can prevent the development of various autoimmune diseases. Lactobacilli are beneficial gut bacteria that play an important role in immune system development. The goals of this study were to assess the ability of three different strains of lactobacilli (<i>L. casei</i> B255, <i>L. reuteri</i> DSM 17509 and <i>L. plantarum</i> LP299v) to control lupus development/progression in (NZBxNZW)F1 (BWF1) lupus-prone mice before and after disease onset, and identify the mechanisms mediating protection. BWF1 mice fed with individual <i>L. casei</i> or <i>L. reuteri</i> before disease onset exhibited delayed lupus onset and increased survival, while feeding <i>L. plantarum</i> had little impact. <i>In vitro</i> treatment of BWF1 dendritic cells with individual lactobacilli strains upregulated IL-10 production to various extents, with <i>L. casei</i> being the most effective. The protection mediated by <i>L. casei</i> was associated with upregulation of B7-1 and B7-2 by antigen presenting cells, two costimulatory molecules important for regulatory T cell (Treg) induction. Moreover, feeding <i>L. casei</i> lead to increased percentages of CD4<sup>+</sup>Foxp3<sup>+</sup> Tregs and IL10-producing T cells in the lymphoid organs of treated mice. More importantly, mice fed <i>L. casei</i> after disease onset remained stable for several months, i.e. exhibited delayed anti-nucleic acid production and kidney disease progression, and increased survival. Therefore, feeding lactobacilli appears to delay lupus progression possibly <i>via</i> mechanisms involving Treg induction and IL-10 production. Altogether, these data support the notion that ingestion of lactobacilli, with immunoregulatory properties, may be a viable strategy for controlling disease development and progression in patients with lupus, i.e. extending remission length and reducing flare frequency.</p>