β-Glucan Curdlan Induces IL-10–Producing CD4+ T Cells and Inhibits Allergic Airway Inflammation

Abstract

A number of studies have suggested a correlation between a decreased incidence in infectious diseases and an increased incidence of allergic diseases, including asthma. Although several pathogen-derived products have been shown to possess therapeutic potential for allergic diseases, it remains largely unknown whether β-glucan, a cell wall component of a variety of fungi, yeasts, and bacteria, has a regulatory potential for allergic diseases. In this study, we examined the effect of curdlan, a linear β-(1-3)-glucan, on the development of allergic airway inflammation. We found that i.p. injection of curdlan significantly inhibited Ag-induced eosinophil recruitment and Th2 cytokine production in the airways. The activation of CD4+ T cells in the presence of curdlan induced IL-10–producing CD4+ T cells with high levels of c-Maf expression. Curdlan-induced development of IL-10–producing CD4+ T cells required the presence of APCs and ICOS/ICOS ligand interaction. Curdlan-induced development of IL-10–producing CD4+ T cells also required intrinsic expression of STAT6. Furthermore, the transfer of Ag-specific CD4+ T cells that were stimulated in the presence of curdlan inhibited Ag-induced eosinophil recruitment into the airways. Taken together, these results suggest that curdlan is capable of inducing IL-10–producing CD4+ T cells and inhibiting the development of eosinohilic airway inflammation, underscoring the therapeutic potential of curdlan for allergic diseases.

Immunomodulatory Glycan Lacto-N-Fucopentaose III Requires Clathrin-Mediated Endocytosis To Induce Alternative Activation of Antigen-Presenting Cells

“…As suggested earlier, the ability of glycans to directly drive alternative activation of APCs may lie in the nature of the glycans. The majority of the studies demonstrating that glycans by themselves activate and mature APCs into anti-inflammatory and Th2-driving phenotypes employed multivalent neoglycoconjugates or naturally occurring ␤-glucans (9,60,61). The results presented here showing that LNFPIII-NGC are taken up and processed via the classical endosomal pathway suggest that signaling originating from endosomes may be the requisite intracellular signaling pathways that multivalent glycans activate to initiate APC polarization to anti-inflammatory and/or Th2-type cells.…”

“…In this regard, we and others demonstrated that glycans found on pathogens in human milk and in certain foods are capable of inducing alternative activation of APCs (9)(10)(11). Glycans on glycoproteins and glycolipids are known to play important roles not only for binding of glycoproteins to receptors on APCs but also in increasing phagocytosis (12)(13)(14)(15).…”

Topical Administration of β-1,3-Glucan to Modulate Allergic Conjunctivitis in a Murine Model

“…14 The ability of intraperitoneally injected BG to modulate allergic airway inflammation through IL-10-secreting CD4 T cells has been demonstrated recently. 15 We also noted that the numbers of IL-10-positive CD4 T cells in draining LNs and the secretion of IL-10 in the in vitro T cell assay significantly increased after topical BG application. Microbial infection or inflammatory mediators stimulate the secretion of inflammatory cytokines, such as IL-17, TGF-b, or IL-27, from antigenpresenting cells that promote the generation of IL-10-producing T cells.…”

“…15,22,26,27 Kearley et al 28 reported that CD4þCD25þ T cells can suppress the Th2 cell-driven response of airway inflammation to allergens in vivo by an IL-10-dependent mechanism. In our data, we observed that BG application induced an increase in the population of Foxp3þ CD4þ CD25þ Treg cells in the draining LNs.…”

“…[16][17][18] In addition, Mendel et al 19 demonstrated that development of IL-10-producing CD4þ T cells depends on IL-4 and signal transducer and activator of transcription-6 (STAT-6), and that STAT6 is important for both the differentiation of Th2 cells and the development of IL-10 producing CD4þ T cells. 15 In addition, Kawashima et al 15 suggested that BG instructs antigen-presenting cells mediated by dectin-1 to induce development of IL-10-producing CD4þ T cells to modulate allergic inflammation.…”