BTLA expression in patients with severe community-acquired pneumonia and the impact of glucocorticoid intervention in animal models

ZHOU Guoqi; WANG Daoxin; LIU Daishun; LIU Zhenfeng; LI Zhaoying

doi:10.13431/j.cnki.immunol.j.20170056

Abstract：In this study,we investigated potential changes in B and T lymphocyte attenuator (BTLA) expressed on lymphocytes and bronchial mucosa in patients with severe community acquired pneumonia (CAP),and to evaluate the effects of BTLA on a model of LPS-induced acute lung inflammation.The ratio of BTLA+CD4+ lymphocytes in human subject was analyzed by flow cytometry;HE staining and immunohistochemical staining were employed to detecl the BTLA in bronchial mucosa from patients with severe CAP.The percentages of circulating BTLA + CD4 + lymphocytes were determined in an LPS-induced acute lung inflammation model.Bronchoalveolar lavage fluid (BALF) was collected from mice and analyzed for leukocyte counts by enzyme-linked immunosorbent assay (ELISA).Lung tissue samples were collected and assessed via Western blotting,immunohistochemistry and HE staining.Data showed that the percentage of circulating BTLA + CD4 + lymphocytes in patients with severe CAP was significantly higher than that in control groups;HE staining showed that there were inflammatory cell infiltration in bronchial mucosa and submucosa,as well as thickening of bronchial walls in patients with severe CAP.Immunohistochemistry for BTLA in bronchial mucosa showed that BTLA protein expression was upregulated in bronchial epithelium and inflammatory cells of patients with severe CAP.The percentage of circulating BTLA+CD4+ lymphocytes were significantly higher in the LPS-induced acute lung inflammation model than that in control groups.Agonistic anti-BTLA antibody 6A6 could upregulate BTLA expression significantly in LPS-induced acute lung inflammation mice.Moreover,the agonistic anti-BTLA antibody 6A6 attenuated inflammatory responses and NF-κB pathway activation in model mice.These results demonstrated that BTLA play an important role in immunoregulation of severe CAP,which may be a therapeutic target for the treatment of severe CAP.Meanwhile,BTLA expression may reflect the body's immune status and guide decisions regarding steroid therapy for treating severe CAP.