B7-H3 participates in the development of Asthma by augmentation of the inflammatory response independent of TLR2 pathway

Abstract

B7-H3, a new member of the B7 superfamily, acts as both a T cell costimulator and coinhibitor. Recent studies identified B7-H3 plays a critical role in the development of asthma. But the definitive mechanism is not clear. In this study, we further report that B7-H3 participates in the development of OVA-induced asthma in a murine model. And study its mechanism through the vitro and vivo experiment. Exogenous administration of B7-H3 strongly amplified the inflammatory response and augmented proinflammatory cytokines in vitro and vivo. These B7-H3–associated proinflammatory effects were not dependent on TLR2 signaling, as airway inflammation, eosinophils infiltration and cytokins (IL-4, IL-5, IL-13 and IFN-gamma) augment were still amplified in TLR2-deficient mice after administrated recombinant mouse B7-H3. These results indicated an important role for B7-H3 in the development of Th1 and Th2 cells in a murine model of asthma and its proinflammatory effects are not dependent on TLR2 signaling.

Evaluation of the role of B7-H3 haplotype in association with impaired B7-H3 expression and protection against type 1 diabetes in Chinese Han population

“…B7-H3 could amplify LPS, NF-κB p65 and MAPK p38 signals and make them participate in monocyte/macrophage-mediated inflammatory responses [26,31]. B7-H3 also participated in the progression of asthma and augmented the inflammatory response independent of the Toll-like receptor 2 (TLR2) pathways [32]. Consistent with the above results, our study indicated the proinflammatory role of B7-H3 in the progression of T1D.…”

Fibronectin enhances tumor metastasis through B7‐H3 in clear cell renal cell carcinoma

“…Initial studies have shown that B7-H3 can selectively promote T cells to secrete IFN-c and can play an important role in the antitumor immune response [32,33]. However, subsequent studies have found that knocking out the B7-H3 molecule can aggravate the inflammatory response, and they confirm that this molecule is mainly involved Th2 subgroup differentiation [7,34]. The main function of B7-H3 is increasingly believed to inhibit T cell immune response, which is a cosuppressive molecule [35,36].…”

The role of miR-29c/B7-H3 axis in children with allergic asthma

“…Besides tumors, B7-H3 also takes parts in inflammatory diseases such as sepsis [ 27 ] and bacterial meningitis [ 28 ]. Our previous studies also demonstrated that B7-H3 plays an important role in the development of asthma by augmentation of the inflammatory response [ 5 , 6 ].…”

“…After a 24 h culture at 37 °C, 5% CO 2 , proliferated T cells were harvested and seeded into 6-well flat-plate that was pre-coated with anti-CD3 mAb (50 ng/ml) and anti-CD28 mAb (500 ng/l). After another 24 h, cell-free supernatants were collected to measure cytokines of IL-4 and IL-17 (pg/ml) using ELISA Kits while cells were collected to measure the relative expression of mRNA of GATA-3 and ROR-γt as previously described [ 6 ].…”

“…Our previous study showed that blockage of B7-H3 could alleviate 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 bronchoalveolar lavage fluid [ 5 ]. Recently, our study demonstrated that B7-H3 could induce GATA-3 and ROR-γt expression in human naïve CD4 + T cells and enhance IL-4 and IL-17 secretion in vitro [ 6 ]. Taken together, these studies indicated that B7-H3 plays an important role in immunopathogenesis of asthma through regulating of Th2 and Th17 differentiation.…”