Expression of B and T Lymphocyte Attenuator in Patients with Severe Community-Acquired Pneumonia and the Effect of Steroid Therapy in a Mouse Model.

BACKGROUND:Severe community-acquired pneumonia (CAP) remains a clinical problem, and the identification of new therapeutic targets may increase the rate of successfully treating patients with severe CAP. B and T lymphocyte attenuator (BTLA) is an immunoglobulin-related membrane protein that may play a vital role in the pathogenesis of infection. However, the effects of BTLA in related to severe CAP involved are unknown. In this study, we investigated potential changes in BTLA expression on lymphocytes in patients with severe CAP and determined how BTLA expression affects a model of LPS-induced acute lung inflammation. METHODS:The percentages of circulating BTLA+CD4+ lymphocytes were determined in patients with severe CAP and in an LPS-induced acute lung inflammation model. Bronchoalveolar lavage fluid (BALF) was collected from mice and analyzed for leukocyte counts and by enzyme-linked immunosorbent assay (ELISA). Lung tissue samples were collected and assessed via Western blotting, immunohistochemistry and HE staining. RESULTS:The percentages of circulating BTLA+CD4+ lymphocytes were significantly higher in patients with severe CAP and in mice with LPS-induced acute lung inflammation than in the control groups. After treatment with either dexamethasone or the agonistic anti-BTLA antibody 6A6, BTLA expression was significantly higher than that in the control mice with LPS-induced acute lung inflammation. Moreover, both dexamethasone and the agonistic anti-BTLA antibody 6A6 attenuated inflammatory responses and nuclear factor (NF)-κB pathway activation. CONCLUSIONS:These results demonstrated that BTLA may be a therapeutic target for the treatment of severe CAP and that BTLA expression may reflect the body's immune status and guide decisions regarding steroid therapy for treating severe CAP.

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