BTLA-expressing CD11c antigen presenting cells in patients with active tuberculosis exhibit low capacity to stimulate T cell proliferation

Wang, Wan Dang; Gao, Yu; Lu, Yuan; Zhang, Jun Ai; Liu, Gan Bin; Kong, Bin; Xiang, Wen Yu; Dai, You Chao; Yu, Shi Yan; Jia, Yan; Fu, Xiao; Yi, Lai; Zheng, Bin; Chen, Zheng W.; Zhong, Jixin; Xu, Jun

doi:10.1016/j.cellimm.2016.09.015

Cited by 19 publications

(28 citation statements)

References 32 publications

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“…During activation, BTLA is not expressed on T helper type 2 (Th2) cells, but Th1 cells. The expression of BTLA on T cells participates in negative regulation of T cell and then leads to an decreased T-lymphocytes proliferation [9]. Recently, many investigations have focused on the relationship of BTLA with inflammation, autoimmune disease and cancer.…”

Section: Introductionmentioning

confidence: 99%

Investigation of BTLA tagging variants with risk of esophagogastric junction adenocarcinoma

et al. 2019

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Background: Variants in B- and T-lymphocyte attenuator (BTLA) gene are likely to affect the function of BTLA protein. Methods: In the present case–control study, we selected BTLA tagging single-nucleotide polymorphisms (SNPs) (rs16859629 T>C, rs1982809 G>A, rs2171513 G>A and rs3112270 A>G) and conducted a case–control study to identify the association of BTLA SNPs with risk of esophagogastric junction adenocarcinoma (EGJA). The present study involved 1236 new incident EGJA cases and 1540 cancer-free controls. Results: The genotypes of BTLA SNPs were analyzed using a SNPscan Kit. No association was also found between the BTLA SNPs and the susceptibility of EGJA in overall comparsion. In subgroup analyses, the BTLA rs1982809 was found to be associated with an increased susceptibility of EGJA (AA versus GG: ORadjusted = 2.09, 95% CI 1.08–4.07, P = 0.030; and AA versus GA/GG: ORadjusted = 1.99, 95% CI 1.04–3.82, P = 0.039). In haplotype comparison, we identified that TAAG haplotype with the order of BTLA rs16859629, rs1982809, rs2171513 and rs3112270 SNPs might increase the susceptibility of EGJA (OR = 3.07, 95% CI = 1.41–6.71; P = 0.003). Conclusion: To conclude, the present study suggests that BTLA Trs16859629Ars1982809Ars2171513Grs3112270 haplotype may increase the susceptibility of EGJA. More studies should be conducted to evaluate whether BTLA polymorphisms may influence the susceptibility of cancer in the future.

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Section: Introductionmentioning

confidence: 99%

Investigation of BTLA tagging variants with risk of esophagogastric junction adenocarcinoma

et al. 2019

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“…In a previous study, we demonstrated that BTLA expression was involved in effector memory functions for αβT cells in patients with active TB (24) and associated with increased Foxp3 expression in CD4 + T cells in dextran sulfate sodium-induced colitis (25). Moreover, we found that BTLA is highly expressed in CD11c-expressing APCs, and is associated with decreased capacity to stimulate allogeneic T cell proliferation (26).…”

Section: Introductionmentioning

confidence: 77%

“…Peripheral blood mononuclear cells (PBMCs) were prepared as described previously (24,26). Blood samples (10 mL) were drawn from each subject in acid citrate dextrose (ACD)containing blood collection tubes.…”

Section: Peripheral Blood Mononuclear Cells Preparationmentioning

confidence: 99%

“…The expression of BTLA, DC maturation markers CD83 and CCR7, DC antigen presenting molecules HLA-DR, and costimulatory molecules CD80 and CD86 on tDCs and DC subsets was determined by flow cytometry (15,26,27). Heparin sodiumanticoagulated whole blood (100 µL) was probed with antibodies for 30 min, followed by lysis of red blood cells.…”

Section: Flow Cytometry Analysismentioning

confidence: 99%

“…Intracellular cytokine staining (ICS) was performed to detect the cytokine secretion by the DCs, as described previously (26)(27)(28). PBMCs (1 × 10 6 ) in round-bottom 96-well plates were used to measure IL-4, IL-6, and TGF-β in mDCs.…”

Section: And Pdc Intracellular Cytokine Stainingmentioning

confidence: 99%

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BTLA-Expressing Dendritic Cells in Patients With Tuberculosis Exhibit Reduced Production of IL-12/IFN-α and Increased Production of IL-4 and TGF-β, Favoring Th2 and Foxp3+ Treg Polarization

Zhang

Wang

et al. 2020

Front. Immunol.

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Little is known about how tuberculosis (TB) impairs dendritic cell (DC) function and anti-TB immune responses. We previously showed that the B and T lymphocyte attenuator (BTLA), an immune inhibitory receptor, is involved in TB pathogenesis. Here, we examined whether BTLA expression in TB affects phenotypic and functional aspects of DCs. Active TB patients exhibited higher expression of BTLA in myeloid dendritic cells (mDCs) and plasmacytoid DCs (pDCs) subsets compared with healthy controls (HCs). BTLA expression was similarly high in untreated TB, TB relapse, and sputum-bacillus positive TB, but anti-TB therapy reduced TB-driven increases in frequencies of BTLA + DCs. BTLA + DCs in active TB showed decreased expression of the DC maturation marker CD83, with an increased expression of CCR7 in mDCs. BTLA + DCs in active TB displayed a decreased ability to express HLA-DR and to uptake foreign antigen, with a reduced expression of the co-stimulatory molecule CD80, but not CD86. Functionally, BTLA + DCs in active TB showed a decreased production of IL-12 and IFN-α as well as a reduced ability to stimulate allogeneic T-cell proliferative responses. BTLA + mDCs produced larger amounts of IL-4 and TGF-β than BTLA − mDCs in both HCs and APT patients. BTLA + DCs from active TB patients showed a reduced ability to stimulate Mtb antigen-driven Th17 and Th22 polarizations as compared to those from HCs. Conversely, these BTLA + DCs more readily promoted the differentiation of T regulatory cells (Treg) and Th2 than those from HCs. These findings suggest that TB-driven BTLA expression in DCs impairs the expression of functional DC surrogate markers and suppress the ability of DCs to induce anti-TB Th17 and Th22 response while promoting Th2 and Foxp3 + Tregs.

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Circular RNA TRAPPC6B inhibits intracellular Mycobacterium tuberculosis growth while inducing autophagy in macrophages by targeting microRNA‐874‐3p

Luo

Zhang

et al. 2021

Clin & Trans Imm

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Objectives Genetic and epigenetic mechanisms regulate antimicrobial immunity against Mycobacterium tuberculosis (Mtb) infection. Methods The present study assessed circular RNA TRAPPC6B (circTRAPPC6B) for antimicrobial immune functions and defined mechanisms wherein circTRAPPC6B regulates Mtb growth, autophagy and microRNA in macrophages. Results The Mtb infection of monocytes/macrophages resulted in a significantly decreased level of circTRAPPC6B that inhibited intracellular Mtb growth in macrophages. Conversely, circTRAPPC6B expression enhanced autophagy or autophagy‐associated protein LC3‐II production in Mtb‐infected macrophages. circTRAPPC6B‐enhanced autophagy aggregation or sequestration was also observed in fluorescence in situ hybridisation (FISH) analysis and confocal imaging. Mechanistically, circTRAPPC6B targets an inhibiting element miR‐874‐3p, as shown by bioinformatics, dual‐luciferase reporter gene analysis and pull‐down assay, respectively. Notably, miR‐874‐3p prohibited autophagy via suppressing autophagy protein ATG16L1 by binding to its 3′‐untranslated region (UTR) in Mtb‐infected macrophages and thus promoting intracellular Mtb growth. Concurrently, circTRAPPC6B enhanced autophagy in Mtb‐infected macrophages by blocking the ability of miR‐874‐3p to inhibit ATG16L1. Thus, circTRAPPC6B antagonises the ability of miR‐874‐3p to suppress ATG16L1 expression and activate and enhance autophagy sequestration to restrict Mtb growth in macrophages. Conclusion The current findings suggested that both circTRAPPC6B and miR‐874‐3p mechanisms can be explored as potential therapeutics against Mtb infection.

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BTLA-expressing CD11c antigen presenting cells in patients with active tuberculosis exhibit low capacity to stimulate T cell proliferation

Cited by 19 publications

References 32 publications

Investigation of BTLA tagging variants with risk of esophagogastric junction adenocarcinoma

Investigation of BTLA tagging variants with risk of esophagogastric junction adenocarcinoma

BTLA-Expressing Dendritic Cells in Patients With Tuberculosis Exhibit Reduced Production of IL-12/IFN-α and Increased Production of IL-4 and TGF-β, Favoring Th2 and Foxp3+ Treg Polarization

Circular RNA TRAPPC6B inhibits intracellular Mycobacterium tuberculosis growth while inducing autophagy in macrophages by targeting microRNA‐874‐3p

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