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

• 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

Background: 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> Methods: Ovalbumin (OVA)-specific Th2 cells were differentiated from naïve CD4⁺ T cells of DO11.10/RAG-2^-/- mice in vitro 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> Results: 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> Conclusions: 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

Keywords

• asthma
• eosinophil
• Mfsd10
• monoclonal antibody
• T cell

Details

• CRID: 1390001204634581248
• NII Article ID: 130004477230
• DOI: 10.2332/allergolint.13-oa-0635
• ISSN: 14401592
• ISSN: 13238930
• Web Site: http://api.elsevier.com/content/article/PII:S1323893015300812?httpAccept=text/xml
• Web Site: http://api.elsevier.com/content/article/PII:S1323893015300812?httpAccept=text/plain
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed