Antibodies and Their Receptors: Different Potential Roles in Mucosal Defense

Horton, Rachel Elizabeth; Vidarsson, Gestur

doi:10.3389/fimmu.2013.00200

Cited by 86 publications

(75 citation statements)

References 111 publications

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“…T cell-dependent and T cell-independent pathways, and secreted immunoglobulins at LP are then transported to the lumen by immunoglobulin receptors (Strugnell and Wijburg, 2010;Horton and Vidarsson, 2013). We showed the lymphocyte populations including intestinal B cells and B220 − IgA + cells (which represent plasma cells) were not significantly different and IgA secreting cells in LP were not also different by using ELISPOT assays (data not shown).…”

Section: Syntenin-1mentioning

confidence: 45%

“…Additionally, recent studies have shown that mucosal IgM and IgG can also provide humoral protection from various pathogens (Horton and Vidarsson, 2013;Saeland et al, 2003;Stapleton et al, 2011). On the other hand, mucosal IgG or IgM production is excessively increased in patients with an inflammatory bowel disease such as ulcerative colitis and Crohn's disease (Helgeland et al, 1992;Macpherson et al, 1996;Thoree et al, 2002).…”

Section: Syntenin-1mentioning

confidence: 98%

“…Mucosal IgA plays crucial roles in host defense and maintenance of normal gut microbiota (Fagarasan et al, 2002;Horton and Vidarsson, 2013;Strugnell and Wijburg, 2010;Suzuki et al, 2004). Additionally, recent studies have shown that mucosal IgM and IgG can also provide humoral protection from various pathogens (Horton and Vidarsson, 2013;Saeland et al, 2003;Stapleton et al, 2011).…”

Section: Syntenin-1mentioning

confidence: 99%

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Increased production of intestinal immunoglobulins in Syntenin-1-deficient mice

et al. 2015

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Syntenin-1 is an intracellular PDZ protein that binds multiple proteins and regulates protein trafficking, cancer metastasis, exosome production, synaptic formation, and IL-5 signaling. However, the functions of Syntenin-1 have not yet been clearly characterized in detail, especially in vivo. In this study, we generated a Syntenin-1 knock out (KO) mouse strain and analyzed the role(s) of Syntenin-1 in IL-5 signaling, because the direct interaction of Syntenin-1 with the cytoplasmic domain of the IL-5 receptor α subunit and the regulation of IL-5 signaling by Syntenin-1 have been reported. Unexpectedly, the number of IL-5-responding cells was normal and the levels of fecal immunoglobulins were rather higher in the Syntenin-1 KO mice. We also found that IgA and IgM production of splenic B cells stimulated in vitro was increased in Syntenin-1 KO mice. In addition, we showed that a distribution of intestinal microbial flora was influenced in Syntenin-1 KO mice. Our data indicate that Syntenin-1 negatively regulates the intestinal immunoglobulin production and has a function to maintain the intestinal homeostasis in vivo. The analysis of Syntenin-1 KO mice may provide novel information on not only mucosal immunity but also other functions of Syntenin-1 such as cancer metastasis and neural development.

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Section: Syntenin-1mentioning

confidence: 45%

Section: Syntenin-1mentioning

confidence: 98%

Section: Syntenin-1mentioning

confidence: 99%

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Increased production of intestinal immunoglobulins in Syntenin-1-deficient mice

et al. 2015

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“…(a), a significant increase in the mean fluorescence intensity value due to parasite‐bound IgA was observed in tachyzoites incubated with IgA‐NcMP/CpG compared with that of parasites incubated with IgA‐CpG, so confirming the specificity of the antibodies raised by immunization. The agglutination of pathogens is one recognized effector function of IgA in the intestinal mucosa, so preventing their attachment to host cells . To assess the agglutinating capacity of the intestinal IgA produced on i.n.…”

Section: Resultsmentioning

confidence: 99%

Protective effect of intranasal immunization with Neospora caninum membrane antigens against murine neosporosis established through the gastrointestinal tract

et al. 2014

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Summary Neospora caninum is an Apicomplexa parasite that in the last two decades was acknowledged as the main pathogenic agent responsible for economic losses in the cattle industry. In the present study, the effectiveness of intranasal immunization with N. caninum membrane antigens plus CpG adjuvant was assessed in a murine model of intragastrically established neosporosis. Immunized mice presented a lower parasitic burden in the brain on infection with 5 × 107 tachyzoites, showing that significant protection was achieved by this immunization strategy. Intestinal IgA antibodies raised by immunization markedly agglutinated live N. caninum tachyzoites whereas previous opsonization with IgG antibodies purified from immunized mice sera reduced parasite survival within macrophage cells. Although an IgG1 : IgG2a ratio < 1 was detected in the immunized mice before and after infection, indicative of a predominant T helper type 1 immune response, no increased production of interferon‐γ was detected in the spleen or mesenteric lymph nodes of the immunized mice. Altogether, these results show that mucosal immunization with N. caninum membrane proteins plus CpG adjuvant protect against intragastrically established neosporosis and indicate that parasite‐specific mucosal and circulating antibodies have a protective role against this parasitic infection.

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“…Neutrophil granulocytes, similar to other leukocytes of myeloid origin, express the FcaRI, which is specific for IgA. However, this receptor has (5,11,12,51), whereas IgA complexed with Ag triggers multiple proinflammatory activities, including neutrophil recruitment, ROS release, and Ab-dependent cytotoxicity (11,12). For subepidermal blistering diseases, only indirect evidence exists for the proinflammatory activity of IgA autoantibodies.…”

Section: Discussionmentioning

confidence: 99%

Recombinant Human IgA1 and IgA2 Autoantibodies to Type VII Collagen Induce Subepidermal Blistering Ex Vivo

Recke

Trog

Pas

et al. 2014

The Journal of Immunology

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Subepidermal autoimmune blistering dermatoses (AIBD) are prototypic autoantibody-mediated diseases. In epidermolysis bullosa acquisita (EBA), an autoimmune disease with severe and chronic skin blistering, autoantibodies are directed against type VII collagen. IgG is the predominant autoantibody isotype of EBA, the pathogenicity of which has been demonstrated in a variety of in vivo and ex vivo disease models. In contrast, there is not much evidence for the pathogenicity of IgA, which may appear as the only autoantibody isotype in some EBA patients. To investigate the pathogenic potential of IgA autoantibodies, we generated chimeric V gene–matched human IgA1, IgA2, and control IgG1 autoantibodies directed against type VII collagen. Immobilized immune complexes containing the rIgA1 and rIgA2 autoantibodies induced the dose-dependent release of reactive oxygen species from neutrophil granulocytes, a precondition for blister formation. Moreover, both rIgA1 and rIgA2 induced leukocyte-dependent dermal–epidermal separation in cryosections of human skin. In contrast with rIgG1, neither rIgA1 nor rIgA2 was capable of inducing complement deposition at the dermal–epidermal junction. Because complement activation is a prerequisite for blister induction, this lack of function compared with IgG1 may be compensated for by the stronger activation of neutrophil granulocytes by both IgA1 and IgA2. For IgG-mediated AIBD, immunoadsorption therapy is a convenient treatment modality for the removal of pathogenic autoantibodies, particularly in treatment-resistant cases. The results of this study show the pathogenic potential of IgA autoantibodies and support the development of adsorber matrices for IgA-mediated AIBD.

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Antibodies and Their Receptors: Different Potential Roles in Mucosal Defense

Cited by 86 publications

References 111 publications

Increased production of intestinal immunoglobulins in Syntenin-1-deficient mice

Increased production of intestinal immunoglobulins in Syntenin-1-deficient mice

Protective effect of intranasal immunization with Neospora caninum membrane antigens against murine neosporosis established through the gastrointestinal tract

Recombinant Human IgA1 and IgA2 Autoantibodies to Type VII Collagen Induce Subepidermal Blistering Ex Vivo

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