BATF Potentially Mediates Negative Regulation of PD-1/PD-Ls Pathway on T Cell Functions in Mycobacterium tuberculosis Infection
| العنوان: | BATF Potentially Mediates Negative Regulation of PD-1/PD-Ls Pathway on T Cell Functions in Mycobacterium tuberculosis Infection |
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| المؤلفون: | Qianqian Liu, Qinfang Ou, Lei Shen, Chao Qiu, Bingyan Zhang, Wenhong Zhang, Lingyun Shao, Yan Gao, Zheng W. Chen |
| المصدر: | Frontiers in Immunology, Vol 10 (2019) Frontiers in Immunology |
| بيانات النشر: | Frontiers Media S.A., 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, T-Lymphocytes, Programmed Cell Death 1 Receptor, Lymphocyte Activation, B7-H1 Antigen, immune response, 0302 clinical medicine, BATF, Immunology and Allergy, RNA, Small Interfering, Original Research, T cell function, Aged, 80 and over, biology, Chemistry, Middle Aged, medicine.anatomical_structure, Basic-Leucine Zipper Transcription Factors, tuberculosis, Host-Pathogen Interactions, Cytokines, Female, Adult, lcsh:Immunologic diseases. Allergy, Adolescent, T cell, Immunology, Context (language use), Peripheral blood mononuclear cell, Immunophenotyping, Mycobacterium tuberculosis, 03 medical and health sciences, Young Adult, Immune system, medicine, Humans, PD-1/PD-Ls pathway, Gene Silencing, Aged, biology.organism_classification, Molecular biology, 030104 developmental biology, Gene Expression Regulation, Cytokine secretion, lcsh:RC581-607, CD8, 030215 immunology |
| الوصف: | Background: Previously, we have found that blockade of PD-1/PD-Ls pathway could enhance CD4+ T cells-mediated protective immunity in patients with active tuberculosis (ATB). However, the mechanism of PD-1/PD-Ls pathway involved in negative regulation of anti-TB immunity has been still unclear. Recently, the study of human immunodeficiency virus (HIV) infection demonstrated that PD-1 could induce the expression of basic leucine zipper ATF-like transcription factor (BATF) to inhibit CD8+ T cell function. While the mechanism of immune regulation of BATF in Mycobacterium tuberculosis (M. tb) infection has not yet been elucidated. Methods: We enrolled 104 participants including ATB patients (n = 66), latent tuberculosis infection (LTBI) (n = 16) and healthy control (HC) (n = 22). The expressions of BATF in peripheral blood CD4+ and CD8+ T cells from enrolled subjects were determined using flow cytometry. Intervention with PD-1/PD-Ls pathway was performed by using blocking antibodies or human PD-L1 fusion protein. Silencing BATF in peripheral blood mononuclear cells (PBMCs) by electroporation with siRNA. Real-time quantitative PCR, CFSE dilution assay and enzyme linked immunosorbent assay (ELISA) were employed to test T cell functions after BATF knockdown. Results: The percentages of BATF+CD4+ (P = 0.0003 and P < 0.0001, respectively) and BATF+CD8+ (P = 0.0003 and P = 0.0003, respectively) cells were significantly increased in ATB patients compared with LTBI and HC. BATF-expressing PD-1+ T cells in CD4+ and CD8+ T cells were much higher in ATB group than those in LTBI group (P = 0.0426 and 0.0104, respectively) and HC group (P = 0.0133 and 0.0340, respectively). There was a positive correlation between BATF expression and PD-1 expression in ATB patients (for CD4+ T cells, r = 0.6761, P = 0.0158; for CD8+ T cells, r = 0.6104, P = 0.0350). BATF knockdown could enhance IL-2 and IFN-γ secretions (P = 0.0485 and 0.0473, respectively) and CD4+ T cells proliferation (P = 0.0041) in vitro. Conclusions: In the context of tuberculosis, BATF mediates negative regulation of PD-1/PD-Ls pathway on T cell functions. BATF knockdown can improve cytokine secretion and cells proliferation in vitro. |
| اللغة: | English |
| تدمد: | 1664-3224 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c475689725850a8480b43e2e328fc3a4Test https://www.frontiersin.org/article/10.3389/fimmu.2019.02430/fullTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c475689725850a8480b43e2e328fc3a4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16643224 |
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