چکیده (انگلیسی):

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 celltransferred
murine eosinophilic inflammation models were comparatively investigated.
Methods: Ovalbumin (OVA)-specific Th2 cells were differentiated from naïve CD4+ T cells of DO11.10RAG-
2-- mice in vitro and cytokine producing activity of the Th2 cells was examined. OVA-immunized and Th2 celltransferred
BALBc 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.