B7-H3 Contributes to the Development of Pathogenic Th2 Cells in a Murine Model of Asthma

Nagashima, Osamu; Harada, Norihiro; Usui, Yoshihiko; Yamazaki, Taiga; Yagita, Hideo; Okumura, Ko; Takahashi, Kazuhisa; Akiba, Hisaya

doi:10.4049/jimmunol.181.6.4062

Cited by 29 publications

(20 citation statements)

References 36 publications

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“…While these data support a role for endogenously expressed B7-H3 to suppress CD4+ T cell responses, several studies employing different antibodies suggest a possible role for B7-H3 in the promotion of Th2 and Th1/CD8 T cell responses. Administration of a B7-H3 mAb reduced airway hypersensitivity by suppressing Th2 cytokine production and decreasing the number of eosinophils in the airway [21]. Furthermore, an independently generated B7-H3 mAb suppressed a CD8+ and CD4+ T cell-mediated contact hypersensitivity [4].…”

Section: Discussionmentioning

confidence: 99%

B7-H3 Promotes Pathogenesis of Autoimmune Disease and Inflammation by Regulating the Activity of Different T Cell Subsets

Luo

Zhu

et al. 2015

PLoS ONE

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B7-H3 is a cell surface molecule in the immunoglobulin superfamily that is frequently upregulated in response to autoantigens and pathogens during host T cell immune responses. However, B7-H3's role in the differential regulation of T cell subsets remains largely unknown. Therefore, we constructed a new B7-H3 deficient mouse strain (B7-H3 KO) and evaluated the functions of B7-H3 in the regulation of Th1, Th2, and Th17 subsets in experimental autoimmune encephalomyelitis (EAE), experimental asthma, and collagen-induced arthritis (CIA); these mouse models were used to predict human immune responses in multiple sclerosis, asthma, and rheumatoid arthritis, respectively. Here, we demonstrate that B7-H3 KO mice have significantly less inflammation, decreased pathogenesis, and limited disease progression in both EAE and CIA mouse models when compared with littermates; these results were accompanied by a decrease in IFN-γ and IL-17 production. In sharp contrast, B7-H3 KO mice developed severe ovalbumin (OVA)-induced asthma with characteristic infiltrations of eosinophils in the lung, increased IL-5 and IL-13 in lavage fluid, and elevated IgE anti-OVA antibodies in the blood. Our results suggest B7-H3 has a costimulatory function on Th1/Th17 but a coinhibitory function on Th2 responses. Our studies reveal that B7-H3 could affect different T cell subsets which have important implications for regulating pathogenesis and disease progression in human autoimmune disease.

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Section: Discussionmentioning

confidence: 99%

B7-H3 Promotes Pathogenesis of Autoimmune Disease and Inflammation by Regulating the Activity of Different T Cell Subsets

Luo

Zhu

et al. 2015

PLoS ONE

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“…The anti-mouse B7-H3-blocking monoclonal Ab (MJ18, rat IgG1) was generated as previously described (Nagashima et al, 2008). The day after tumour implantation, mAb treatment was started.…”

Section: Animal Experimental Protocolmentioning

confidence: 99%

Clinical importance of B7-H3 expression in human pancreatic cancer

et al. 2009

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BACKGROUND: B7-H3 is a new member of the B7 ligand family and regulates T-cell responses in various conditions. However, the role of B7-H3 in tumour immunity is largely unknown. The purpose of this study was to evaluate the clinical significance of B7-H3 expression in human pancreatic cancer and the therapeutic potential for cancer immunotherapy. METHODS: We investigated B7-H3 expression in 59 patients with pancreatic cancer by immunohistochemistry and real-time PCR. Furthermore, we examined the anti-tumour effect of B7-H3-blocking monoclonal antibody in vivo in a murine pancreatic cancer model. RESULTS: Tumour-related B7-H3 expression was abundant in most human pancreatic cancer tissues and was significantly higher compared with that in non-cancer tissue or normal pancreas. Moreover, its expression was significantly more intense in cases with lymph node metastasis and advanced pathological stage. B7-H3 blockade promoted CD8 þ T-cell infiltration into the tumour and induced a substantial anti-tumour effect on murine pancreatic cancer. In addition, the combination of gemcitabine with B7-H3 blockade showed a synergistic anti-tumour effect without overt toxicity. CONCLUSION: Our data show for the first time that B7-H3 may have a critical role in pancreatic cancer and provide the rationale for developing a novel cancer immunotherapy against this fatal disease.

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“…The ligand of B7-H3 is still unknown but seems to be present at the surface of activated T cells [40]. A recent study proposed that B7-H3 supports the differentiation of TH2 cells during sensitization in animal models of asthma, as blocking B7-H3 with an antibody results in a decreased production of TH2 cytokines in draining lymph nodes, reduced infiltration of eosinophils in lungs and in reduced AHR [59]. In contrast, administration of blocking B7-H3 antibody during the sensitization phase increases the severity of allergic conjunctivitis in mice, possibly by inducing IL-5 production in the spleen [60].…”

Section: Involvement Of the B7:cd28 Family Molecules In The Regulatiomentioning

confidence: 99%

The Role of Costimulatory Molecules in Allergic Disease and Asthma

Lombardi

Singh

Akbari³

2009

Int Arch Allergy Immunol

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The prevalence of allergic diseases has increased rapidly in recent years. It is well established that the deleterious allergic response is initiated by T-cell recognition of major histocompatibility class II-peptide complexes at the surface of antigen-presenting cells. While this first signal gives antigen specificity to the adaptive immune response, a second nonspecific costimulatory signal is required by T cells to become fully activated. This signal is provided by interactions between antigen-presenting cells and T cells through molecules borne at the surfaces of the two cell types. Depending on the type of molecules involved, this secondary signal can promote the development of an inflammatory allergic reaction or may favor immune regulation. Several molecules of the B7 family (CD80, CD86, PD-1, ICOS, CTLA-4) and tumor necrosis factor receptor family (OX40, CD30, 4-1BB, Fas, CD27, CD40) play an important role in delivering costimulatory signals in early and late phases of allergic response. Therefore, costimulatory molecules involved in promotion or prevention of allergic immune responses are potential targets for the development of novel therapeutic approaches. This review aims to recapitulate our current understanding of the relationship between allergic diseases and costimulatory molecules.

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B7-H3 Contributes to the Development of Pathogenic Th2 Cells in a Murine Model of Asthma

Cited by 29 publications

References 36 publications

B7-H3 Promotes Pathogenesis of Autoimmune Disease and Inflammation by Regulating the Activity of Different T Cell Subsets

B7-H3 Promotes Pathogenesis of Autoimmune Disease and Inflammation by Regulating the Activity of Different T Cell Subsets

Clinical importance of B7-H3 expression in human pancreatic cancer

The Role of Costimulatory Molecules in Allergic Disease and Asthma

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