Fungal β-glucan, a Dectin-1 ligand, promotes protection from type 1 diabetes by inducing regulatory innate immune response.
نویسندگان
چکیده
β-Glucans are naturally occurring polysaccharides in cereal grains, mushrooms, algae, or microbes, including bacteria, fungi, and yeast. Immune cells recognize these β-glucans through a cell surface pathogen recognition receptor called Dectin-1. Studies using β-glucans and other Dectin-1 binding components have demonstrated the potential of these agents in activating the immune cells for cancer treatment and controlling infections. In this study, we show that the β-glucan from Saccharomyces cerevisiae induces the expression of immune regulatory cytokines (IL-10, TGF-β1, and IL-2) and a tolerogenic enzyme (IDO) in bone marrow-derived dendritic cells as well as spleen cells. These properties can be exploited to modulate autoimmunity in the NOD mouse model of type 1 diabetes (T1D). Treatment of prediabetic NOD mice with low-dose β-glucan resulted in a profound delay in hyperglycemia, and this protection was associated with increase in the frequencies of Foxp3(+), LAP(+), and GARP(+) T cells. Upon Ag presentation, β-glucan-exposed dendritic cells induced a significant increase in Foxp3(+) and LAP(+) T cells in in vitro cultures. Furthermore, systemic coadministration of β-glucan plus pancreatic β cell Ag resulted in an enhanced protection of NOD mice from T1D as compared with treatment with β-glucan alone. These observations demonstrate that the innate immune response induced by low-dose β-glucan is regulatory in nature and can be exploited to modulate T cell response to β cell Ag for inducing an effective protection from T1D.
منابع مشابه
Fungal b-Glucan, a Dectin-1 Ligand, Promotes Protection from Type 1 Diabetes by Inducing Regulatory Innate Immune Response
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ورودعنوان ژورنال:
- Journal of immunology
دوره 193 7 شماره
صفحات -
تاریخ انتشار 2014