Alteration of Immune Responses by N-acetylglucosaminyltransferase V during Allergic Airway Inflammation

Abstract

β-1,6-N-acetylglucosaminyltransferase V (Mgat5 or GlcNac-TV), which is involved in the glycosylation of proteins, is known to be important for down-regulation of TCR-mediated T-cell activation and negatively regulates induction of contact dermatitis and experimental autoimmune encephalomyelitis. However, the role of Mgat5 in the induction of allergic airway inflammation remains unclear. To elucidate the role of Mgat5 in the pathogenesis of allergic airway inflammation, ovalbumin (OVA)-induced airway inflammation was induced in Mgat5-deficient mice. The OVA-specific lymphocyte proliferation and cytokine production levels, OVA-specific IgG1, IgG2a and IgE levels in the serum, and the number of leukocytes and cytokine levels in the bronchoalveolar lavage (BAL) fluid were compared between wild-type and Mgat5-deficient mice. OVA-specific lymphocyte proliferation and production of IFN-γ and IL-10, but not IL-4, were increased in Mgat5-deficient mice, suggesting that Th2-type immune responses are seemed to be suppressed by increased IFN-γ and IL-10 production in these mice. However, Th2-type responses such as OVA-specific IgG1, but not IgE, and IL-5 levels in BAL fluids were increased in Mgat5-deficient mice. Meanwhile, the number of eosinophils was normal, but the numbers of neutrophils, macrophages and lymphocytes were reduced, in these mutant mice during OVA-induced airway inflammation. Mgat5-dependent glycosylation of proteins can modulate acquired immune responses, but it is not essential for the development of OVA-induced eosinophilic airway inflammation.