Selective Suppression of Th2 Cell-Mediated Lung Eosinophilic Inflammation by Anti-Major Facilitator Super Family Domain Containing 10 Monoclonal Antibody

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Author(s)

    • Nishimura Tomoe
    • Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science
    • Saeki Mayumi
    • Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science
    • Motoi Yuji
    • Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science
    • Kitamura Noriko
    • Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science
    • Mori Akio
    • Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital
    • Kaminuma Osamu
    • Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science
    • Hiroi Takachika
    • Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science

Abstract

<b>Background:</b> The eosinophil is deeply associated with the pathogenesis of bronchial asthma and other allergic diseases. We recently identified a novel eosinophil-specific cell surface molecule, major facilitator super family domain containing 10 (Mfsd10). A monoclonal antibody (mAb) against Mfsd10 (M2) showed selective binding and neutralizing activities for eosinophils. However, the relative potency of the blockage of Mfsd10 and other eosinophil-specific molecules for the treatment of allergic diseases has not been evaluated. Therefore, in this study, the effects of M2 and an anti-Siglec-F mAb on antigen-immunized and antigen-specific Th2 cell-transferred murine eosinophilic inflammation models were comparatively investigated.<br> <b>Methods:</b> Ovalbumin (OVA)-specific Th2 cells were differentiated from naïve CD4<sup>+</sup> T cells of DO11.10/RAG-2<sup>-/-</sup> mice <i>in vitro</i> and cytokine producing activity of the Th2 cells was examined. OVA-immunized and Th2 cell-transferred BALB/c mice were treated with M2 or anti-Siglec-F and challenged with OVA. Then the number of inflammatory cells and the concentration of IL-5 in the bronchoalveolar lavage fluid (BALF) were determined.<br> <b>Results:</b> Antigen-specific Th2 cells produced large amounts of IL-4, IL-5 and IL-13 but not IL-17A or IFN-γ. Administration of M2 significantly suppressed antigen-induced lung eosinophil infiltration both in OVA-immunized and Th2 cell-transferred mice. The potency as well as selectivity of M2 for down-regulating eosinophils was quite similar to that of anti-Siglec-F. Both mAbs did not affect antigen-induced IL-5 production in the lungs.<br> <b>Conclusions:</b> Mfsd10 as well as Siglec-F could be an effective target to treat eosinophil-related disorders including bronchial asthma.<br>

Journal

  • Allergology International

    Allergology International 63(Supplement.1), S29-S35, 2014

    Japanese Society of Allergology

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