1.
Immunomodulatory Dual-Sized Microparticle System Conditions Human Antigen Presenting Cells Into a Tolerogenic Phenotype In Vitro and Inhibits Type 1 Diabetes-Specific Autoreactive T Cell Responses.
Brusko, MA, Stewart, JM, Posgai, AL, Wasserfall, CH, Atkinson, MA, Brusko, TM, Keselowsky, BG
Frontiers in immunology. 2020;:574447
Abstract
Current monotherapeutic agents fail to restore tolerance to self-antigens in autoimmune individuals without systemic immunosuppression. We hypothesized that a combinatorial drug formulation delivered by a poly-lactic-co-glycolic acid (PLGA) dual-sized microparticle (dMP) system would facilitate tunable drug delivery to elicit immune tolerance. Specifically, we utilized 30 µm MPs to provide local sustained release of granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor β1 (TGF-β1) along with 1 µm MPs to facilitate phagocytic uptake of encapsulated antigen and 1α,25(OH)2 Vitamin D3 (VD3) followed by tolerogenic antigen presentation. We previously demonstrated the dMP system ameliorated type 1 diabetes (T1D) and experimental autoimmune encephalomyelitis (EAE) in murine models. Here, we investigated the system's capacity to impact human cell activity in vitro to advance clinical translation. dMP treatment directly reduced T cell proliferation and inflammatory cytokine production. dMP delivery to monocytes and monocyte-derived dendritic cells (DCs) increased their expression of surface and intracellular anti-inflammatory mediators. In co-culture, dMP-treated DCs (dMP-DCs) reduced allogeneic T cell receptor (TCR) signaling and proliferation, while increasing PD-1 expression, IL-10 production, and regulatory T cell (Treg) frequency. To model antigen-specific activation and downstream function, we co-cultured TCR-engineered autoreactive T cell "avatars," with dMP-DCs or control DCs followed by β-cell line (ßlox5) target cells. For G6PC2-specific CD8+ avatars (clone 32), dMP-DC exposure reduced Granzyme B and dampened cytotoxicity. GAD65-reactive CD4+ avatars (clone 4.13) exhibited an anergic/exhausted phenotype with dMP-DC presence. Collectively, these data suggest this dMP formulation conditions human antigen presenting cells toward a tolerogenic phenotype, inducing regulatory and suppressive T cell responses.
2.
Association between Bioactive Molecules in Breast Milk and Type 1 Diabetes Mellitus.
Yahaya, T, Shemishere, U
Sultan Qaboos University medical journal. 2020;(1):e5-e12
Abstract
The association between breastfeeding and type 1 diabetes mellitus (T1DM) is controversial. However, several recent studies have established a link between these two factors, necessitating a need to review this subject to raise public awareness. Current research indicates that breast milk contains a variety of bioactive substances including immunoglobulins, oligosaccharides, insulin, lactoferrin, lysozyme, cytokines, epidermal growth factors, leukocytes, nucleotides, beneficial bacteria and vitamins. Such substances strengthen the breastfeeding infant's immune system, both directly, by increasing gut microbiota diversity and attacking harmful bacteria and pro-inflammatory molecules, and indirectly, by increasing thymus performance. Accordingly, a lack of or inadequate breastfeeding may predispose infants to several autoimmune disorders, including T1DM. Nursing mothers and caregivers are therefore advised to follow optimal breastfeeding practices prior to introducing complementary foods.
3.
Effects of probiotic administration on immune responses of children and adolescents with type 1 diabetes to a quadrivalent inactivated influenza vaccine.
Bianchini, S, Orabona, C, Camilloni, B, Berioli, MG, Argentiero, A, Matino, D, Alunno, A, Albini, E, Vacca, C, Pallotta, MT, et al
Human vaccines & immunotherapeutics. 2020;(1):86-94
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Abstract
This study was planned to evaluate whether a 3-month treatment with Lactobacillus rhamnosus GG (LGG) can modify immune system functions in children and adolescents with type 1 diabetes (T1D), leading to an increased immune response to an injectable quadrivalent inactivated influenza vaccine (QIV). A total of 87 pediatric patients with T1D were screened, although 34 patients in the Probiotic group and 30 in the Control group accepted to be vaccinated with QIV and completed the study. Vaccine immunogenicity and safety and the inflammatory cytokine response were studied. Results showed that QIV was immunogenic and safe in T1D pediatric patients and pre-administration of LGG for three months did not substantially modify the QIV humoral immunity. The combination of QIV and LGG reduced inflammatory responses (i.e., IFN-γ, IL17A, IL-17F, IL-6, and TNF-α) from activated PBMCs of pediatric patients with T1D, without dampening the production of seroprotective antibodies. In conclusion, QIV is associated with an adequate immunogenicity in children and adolescents with T1D in presence of a good safety profile. Although a systematic administration of LGG did not result in an improvement of humoral responses to an influenza vaccine, the probiotic did induce important anti-inflammatory effects.