title: Selective suppression of Th2 cell-mediated lung eosinophilic inflammation by anti-major facilitator super family domain containing 10 monoclonal antibody.
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.
  
  
  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.
  
  
  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.
  
  
  CONCLUSIONS
  Mfsd10 as well as Siglec-F could be an effective target to treat eosinophil-related disorders including bronchial asthma.
authors.affiliation: Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Tomoe
authors.initials: T
authors.lastname: Nishimura
authors.affiliation: Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Saeki
authors.affiliation: Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Motoi
authors.affiliation: Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Kitamura
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Kanagawa, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Mori
authors.affiliation: Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Kaminuma
authors.affiliation: Allergy and Immunology Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors.forename: Takachika
authors.initials: T
authors.lastname: Hiroi
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D015848:Interleukin-5 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors* / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D011657:Pulmonary Eosinophilia / Q000188:drug therapy / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015214:Antigens, Differentiation, Myelomonocytic; D007166:Immunosuppressive Agents; D015848:Interleukin-5; D008565:Membrane Proteins; C577305:Mfsd10 protein, mouse; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C443130:Siglecf protein, mouse