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: Tomoe Nishimura, Mayumi Saeki, Yuji Motoi, Noriko Kitamura, Akio Mori, Osamu Kaminuma, Takachika Hiroi
• Journal: Allergology international : official journal of the Japanese Society of Allergology (Allergol Int) Vol. 63 Suppl 1 Pg. 29-35 (May 2014) ISSN: 1440-1592 [Electronic] England
• PMID: 24809373 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antigens, Differentiation, Myelomonocytic
• Immunosuppressive Agents
• Interleukin-5
• Membrane Proteins
• Mfsd10 protein, mouse
• Sialic Acid Binding Immunoglobulin-like Lectins
• Siglecf protein, mouse

Topics

• Animals
• Antibodies, Monoclonal (immunology, pharmacology)
• Antigens, Differentiation, Myelomonocytic (immunology)
• Disease Models, Animal
• Eosinophils (immunology)
• Female
• Immunosuppressive Agents (pharmacology)
• Interleukin-5 (biosynthesis)
• Lymphocyte Activation (immunology)
• Membrane Proteins (antagonists & inhibitors, immunology)
• Mice
• Mice, Knockout
• Pulmonary Eosinophilia (drug therapy, genetics, immunology, pathology)
• Sialic Acid Binding Immunoglobulin-like Lectins
• Th2 Cells (immunology, metabolism)