A Probiotic Mixture Regulates T Cell Balance and Reduces Atopic Dermatitis Symptoms in Mice

Abstract

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with a complex etiology involving the immune response. Recent studies have demonstrated the role of certain probiotics in the treatment and prevention of AD. However, the mechanism by which these probiotics regulate the immune system remains unclear. In this study, we examined the immunomodulatory capacity of Duolac ATP, a mixed formulation of probiotics, both in vitro and in vivo. Results showed that the expression of programmed death-ligand 1(PD-L1) was significantly upregulated on bone marrow-derived dendritic cells (BMDCs) treated with Duolac ATP. Furthermore, the anti-inflammatory cytokines IL-10 and TGF-beta were both upregulated when BMDCs were treated with Duolac ATP. The percentage of proliferated regulatory T cells (Tregs) was enhanced when CD4+ T cells were co-cultured with Duolac ATP-treated BMDCs on plates coated with anti-CD3/CD28 antibodies. Intriguingly, IL-10 secretion from CD4+ T cells was also observed. The AD symptoms, histologic scores, and serum IgE levels in AD mice were significantly decreased after oral treatment with Duolac ATP. Moreover, the Th1-mediated response in AD-induced mice treated with oral Duolac ATP showed upregulation of IL-2 and IFN-gamma as well as of downstream signaling molecules T-bet, STAT-1, and STAT-4. Conversely, Duolac ATP suppressed Th2 and Th17 responses in AD-like mice, as evidenced by the downregulation of GATA-3, C-maf, IL-4, IL-5, and IL-17. Additionally, Duolac ATP increased the number of Tregs found at Peyer’s patches (PP) in treated AD mice. These results suggest that Duolac ATP modulates DCs to initiate both Th1 and Treg responses in AD mice. Thus, Duolac ATP represents a potential preventative agent against AD and could serve as an effective immunomodulator in AD patients.

Galectin-9 Induced by Dietary Probiotic Mixture Regulates Immune Balance to Reduce Atopic Dermatitis Symptoms in Mice

“…AD is triggered by hypersensitivity of the Th2 response, which can be overcome by rebalancing CD4 + T cell subsets (25). To determine whether YK4 administration affects intestinal and systemic T cell responses, subpopulations of CD4 + T cells in mLN, PP, and the spleen obtained using the gating strategy shown in Figure 2A were examined in AD mice with/without YK4 administration.…”

“…In addition, L. plantarum WCFS1 induced CD103 + DCs infiltration and generation of Tregs in the spleen (24). Duolac ATP, a mixture of four probiotic strains; i.e., Lactobacillus casei CBT LC5, Lactobacillus plantarum CBT LP3, Lactobacillus rhamnosus CBT LR5, and Bifidobacterium lactis CBT BL3, was reported to modulate the expression of costimulatory molecules of DCs and downregulate Th2 responses in an AD mouse model (25). Mixed probiotic strains of Lactobacillus and Bifidobacterium reduced the atopic dermatitis index in young AD patients (26) and an AD mouse model (27,28).…”

Traiter la dermatite atopique par les probiotiques

“…Les mécanismes permettant l'atténuation des symptômes de la DA ont été étudiés par ces mêmes équipes de recherche et l'implication de cellules dendritiques (CD) tolérogènes a été mise en évidence [5][6][7][8]. En effet, lorsque des CD de souris atteintes de DA sont traitées par des probiotiques, une augmentation des marqueurs spécifiques des CD tolérogènes est observée [5][6][7][8].…”

“…Les CD tolérogènes sont en effet caractérisées par l'expression de certains marqueurs tels que PD-L1 (programmed death-ligand 1), ICOS (inducible T-cell costimulator), iDO (indoléamine 2-3 dioxygénase 1), et par la production de cytokines anti-inflammatoires comme l'IL-10 et le TGF-β (transforming growth factor-beta) [5][6][7][8]. De plus, in vitro, la co-culture de ces CD tolérogènes induites par les probiotiques avec des lymphocytes T CD4 + entraine leur différenciation en lymphocytes T régulateurs (Treg) [5][6][7][8]. Ainsi, c'est par l'induction de Treg dans les ganglions mésentériques bordant les intestins que les CD tolérogènes participent à la résolution de l'inflammation et au rétablissement de l'homéostasie cutanée ( Figure 1…”

Pilot evaluation of Enterococcus faecium SF68 as adjunctive therapy for oclacitinib‐responsive adult atopic dermatitis in dogs

“…Multiple mechanisms through which probiotics impact the immune system have been proposed, including, but not limited to, induction of regulatory cytokines interleukin (IL)-10, transforming growth factor-beta, IL-12 and interferon-gamma that downregulate Th2 cytokines. As demonstrated in human serum and rodent tissue models, this subsequently induces ttp://www.bsava.com/ Journal of Small Animal Practice • Vol 60 • August 2019 • © 2019 British Small Animal Veterinary Association oral tolerance, facilitates T cell differentiation, maturation and prevents allergic inflammation (Bermudez-Brito et al 2012, Mccusker & Sidbury 2016, Cross et al, 2001, Kalliomäki et al 2001, Kim et al 2018, Inoue et al 2014). The addition of lactic acid-producing bacterium has been investigated in children, adults and young dogs to prevent and alleviate the symptoms of AD (Inoue et al 2014, Kalliomäki et al 2001, Kalliomäki et al 2003, Isolauri et al 2000., Marsella 2009, Marsella et al 2012.…”