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

• Published in: Annals of allergy, asthma, & immunology Vol. 111; no. 4; pp. 276 - 281
• Main Authors: Chen, Zheng-Rong, Zhang, Guang-Bo, Wang, Yu-Qing, Yan, Yong-Dong, Zhou, Wei-Fang, Zhu, CanHong, Chen, Ying, Wang, Jian, Ji, Wei
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2013
• Subjects: Allergy and Immunology; Animals; Anti-Asthmatic Agents - pharmacology; Anti-Asthmatic Agents - therapeutic use; Antibodies, Monoclonal - pharmacology; Antibodies, Monoclonal - therapeutic use; Asthma - drug therapy; Asthma - immunology; B7 Antigens - immunology; Bronchoalveolar Lavage Fluid - chemistry; Bronchoalveolar Lavage Fluid - cytology; Cytokines - immunology; Disease Models, Animal; Female; Immunoglobulin G - immunology; Leukocyte Count; Mice; Mice, Inbred BALB C; Ovalbumin - immunology; Th1 Cells - immunology; Th17 Cells - immunology; Th2 Cells - immunology
• ISSN: 1081-1206; 1534-4436; 1534-4436
• DOI: 10.1016/j.anai.2013.06.030

B7 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 B7 family member, plays a critical role in the development of Th2 cells. To investigate the effects of anti–B7-H3 monoclonal antibody (mAb) in a mouse model of allergic asthma. 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-17 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. 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-17 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. Blockade of B7-H3 signals may provide a novel therapeutic approach to the treatment of allergic asthma.