Immunity & infection

Oral

Iga Deficiency Induces Spontaneous Inflammation in the Ileum

Wednesday, June 14
6:15 PM - 7:45 PM

Background & Aim: Immunoglobulin (Ig) A is known to be involved in the maintenance of mucosal homeostasis. It has been reported that deficiency of activation-induced cytidine deaminase results in aberrant composition of commensal flora in the gut. However, it is still unclear whether such phenotype was directly caused by the lack of secreted IgA. Therefore we created an animal model of IgA deficiency (IgA-/-) by using the CRISPR/Cas9 system.


Methods & Results: The guide RNAs specific for IgE and IgA cytoplasmic domains and Cas9 mRNA were injected into C57BL/6 zygotes. PCR products corresponding for the region between IgE and IgA tails from the offsprings were applied for sequencing. Subsequently we found that one of them had a deletion of over 5kb region coding the entire IgA allele and thus identified as IgA-/-. To characterize this line, we analyzed the histopathology at 12 weeks old. Although there were no significant changes in most of organs, we found irritated mucosa at the ileum compared to the littermate control. Flow cytometry analysis showed increased CD4+ T cells in the intestinal lamina propria associated with increased production of IFN-γ and IL-17 in the IgA-/-. Furthermore, scanning electron microscopy revealed an increase of segmented filamentous bacteria on the ileal epithelia in the IgA-/- compared to the control.


Conclusion: Our current results imply that the lack of IgA may induce disregulated mucosal homeostasis in the gut and altered commensal flora in the intestine. Additional experiments are currently ongoing.

Takashi Nagaishi

Tokyo Medical and Dental University, Department of Gastroenterology

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    Taro Watabe

    Tokyo Medical and Dental University, Department of Gastroenterology

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      Nisha Jose

      Tokyo Medical and Dental University, Department of Gastroenterology

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        Akinori Hosoya

        Tokyo Medical and Dental University, Department of Gastroenterology

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          Yudai Kojima

          Tokyo Medical and Dental University, Department of Gastroenterology

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            Naoya Tsugawa

            Tokyo Medical and Dental University, Department of Gastroenterology

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              Takahiro Adachi

              Tokyo Medical and Dental University, Department of Immunology

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                Mamoru Watanabe

                Tokyo Medical and Dental University, Department of Gastroenterology

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