Therapeutic effects of anti-B7-H3 antibody in an ovalbumin-induced mouse asthma model

摘要

Background B& molecules play a key role in regulating allergen-induced T cell activation in asthma, which may occur through T cell recruitment and T helper cell differentiation on allergen provocation. Initial studies have shown that B7-H3 (CD276), a recently identified B& family member, plays a critical role in the development of Th2 cells. Objective To investigate the effects of anti-B7-H3 monoclonal antibody (mAb) in a mouse model of allergic asthma. Methods The asthma model was established by ovalbumin (OVA) sensitization and challenging in female BALB/c mice. Total cell numbers in bronchoalveolar lavage fluid (BALF) were determined, and the expression levels of interferon gamma (IFN-γ), interleukin (IL)-4, and IL-1& in BALF were measured by enzyme-linked immunosorbent assay. Pulmonary eosinophil infiltration and mucus production were detected by hematoxylin and eosin (H&E) and periodic acid-Schiff (PAS), respectively. B7-H3 expression was detected by immunohistochemistry in frozen tissue sections. Results Anti-B7-H3 mAb treatment alleviated the asthmatic syndrome, decreased the levels of B7-H3-positive cells in the lung tissues, abrogated hypercellularity, eosinophil infiltration, and mucus production, and inhibited IL-4 and IL-1& production in BALF at the induction phase as compared with the immunoglobulin G (IgG) control group (P <.01). In addition, the treatment of anti-B7-H3 mAb at the induction phase could increase the expression levels of IFN-γ as compared with the IgG control group (P <.01). Anti-B7-H3 mAb treatment at the effector phase did not inhibit the asthma response. Conclusion Blockade of B7-H3 signals may provide a novel therapeutic approach to the treatment of allergic asthma.