Impairment of Wnt/β-catenin signaling in blood cells of patients with severe cavitary pulmonary tuberculosis

Fan, Lin; Shen, Hongbo; Huang, Huichang; Yang, Rui; Yao, Lan

doi:10.1371/journal.pone.0172549

Cited by 11 publications

(10 citation statements)

References 26 publications

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“…The present TB study showed that β -catenin in both CD4 + and CD8 + T cells had a close association with the regulation of TB progress. Increased β -catenin can enhance the expression of Th1 responses in the CD4 + T population, which is consistent with our previous study [ 15 ]. Interestingly, the frequency of IFN- γ in CD4 + T cells was significantly increased in PBMCs of PTB patients after LiCl stimulation compared with before LiCl stimulation ( Figure 5(c) ), while IFN- γ measurements by ELISA of PTB patients' PBMCs did not show differences between before and after LiCl stimulation ( Figure 5(e) ), indicating that increased β -catenin did not enhance the whole IFN- γ secretion but IFN- γ secretion from some kinds of cells such as CD4 + T cells in the PBMCs of PTB patients.…”

Section: Discussionsupporting

confidence: 93%

“…Thus, the protein level of β -catenin in the whole cell can be associated with the activation of the canonical Wnt/ β -catenin pathway. Our previous study showed that β -catenin mRNA in CD14 − cells was impaired in severe PTB patients, and stimulation of β -catenin could enhance the activation of CD4 + T cells in the blood of PTB [ 15 ]. In the present study, the frequency of CD4 + T cells in conditional Ctnnb1 −/− infected mice was decreased, indicating a role of β -catenin in the activation and proliferation of CD4 + T cells of hosts infected with TB.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous studies [ 14 ] showed impaired IFN- γ expression and decreased CD4 + T cells in the blood of patients with severe cavitary PTB. A further study [ 15 ] indicated that β -catenin might be involved in the impaired IFN- γ expression, Th1 immune response of the host against TB, and mRNA of β -catenin, and TCF-7 was impaired in the CD14 − cells in the blood of patients with severe cavitary PTB.…”

Section: Introductionmentioning

confidence: 99%

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The Role of β-Catenin in Th1 Immune Response against Tuberculosis and Profiles of Expression in Patients with Pulmonary Tuberculosis

Xiong

Niu

Zheng

et al. 2021

Journal of Immunology Research

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β-Catenin is a key molecule of canonical Wnt/β-catenin pathway. Its roles and expression profiles in T cells of tuberculosis (TB) remain unclear. The aim of this study was to explore the role of β-catenin in CD4+ T cells and its expression characteristics in patients with pulmonary tuberculosis (PTB). In this study, CD4+ T cell-specific β-catenin conditional knockout mice (β-CAT-cKO mice) were aerosol infected with Mycobacteria tuberculosis (Mtb) H37RV with wild-type mice as controls. Four weeks after infection, the mRNA expression of IFN-γ, TNF-α, and TCF-7 in the lungs of mice was measured. CD4, CD8, β-catenin, IFN-γ, and TNF-α in mononuclear cells from the lungs and spleens were measured by flow cytometry, and the pathological changes of lungs were also observed. Patients with PTB were enrolled, with blood samples collected and PBMCs isolated. The expressions of β-catenin, IFN-γ, TNF-α, and PD-1 in CD4+ and CD8+ T cells were measured by flow cytometry. Results showed a decreased frequency of and reduced IFN-γ/TNF-α mRNA expression and secretion by CD4+ T cells in the lungs of infected β-CAT-cKO mice compared with infected wild-type controls, and only slightly more inflammatory changes were observed in the lungs. β-catenin expressions in CD4+ and CD8+ T cells were significantly decreased in blood cells of patients with severe PTB compared with those in mild PTB. The stimulation of peripheral blood mononuclear cells (PBMCs) with lithium chloride (LiCl), a stimulant of β-catenin, resulted in the increase in CD4+ T cell frequency, as well as their secretion of IFN-γ and TNF-α. β-Catenin demonstrated a moderately positive correlation with PD-1 in CD4+ T cells. β-Catenin along with PD-1 and IFN-γ in CD4+ T cells had a high correlation with those in CD8+ T cells. In conclusion, β-catenin may be involved in the regulation of Th1 response and CD4+ T cell frequency in TB.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The Role of β-Catenin in Th1 Immune Response against Tuberculosis and Profiles of Expression in Patients with Pulmonary Tuberculosis

Xiong

Niu

Zheng

et al. 2021

Journal of Immunology Research

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“…It is therefore critical to maintain the cellular immune response balance. 4 To achieve this balance, the host uses some strategies, such as producing cytokines, to monitor and mediate effector cell function. 5 Cytokines are important in cell signaling and can affect the behavior of adjacent cells.…”

Section: Introductionmentioning

confidence: 99%

The crucial roles of Th17-related cytokines/signal pathways in M. tuberculosis infection

2017

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Interleukin-17 (IL-17), IL-21, IL-22 and IL-23 can be grouped as T helper 17 (Th17)-related cytokines because they are either produced by Th17/Th22 cells or involved in their development. Here, we review Th17-related cytokines/Th17-like cells, networks/signals and their roles in immune responses or immunity against Mycobacterium tuberculosis (Mtb) infection. Published studies suggest that Th17-related cytokine pathways may be manipulated by Mtb microorganisms for their survival benefits in primary tuberculosis (TB). In addition, there is evidence that immune responses of the signal transducer and activator of transcription 3 (STAT3) signal pathway and Th17-like T-cell subsets are dysregulated or destroyed in patients with TB. Furthermore, Mtb infection can impact upstream cytokines in the STAT3 pathway of Th17-like responses. Based on these findings, we discuss the need for future studies and the rationale for targeting Th17-related cytokines/signals as a potential adjunctive treatment.

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“…Flow cytometry was performed as described in the other reports [26,27]. 0.1 Million H1975 cells was rstly plated in 24-well-plate.…”

Section: Intracellular Cytokine Staining (Ics) For T Cell Activation mentioning

confidence: 99%

Bi-specific Antibody Y111, Targeting PD-L1 and CD3 Considerably Enhances the Therapeutic Efficacy of Adoptive Transferred Vγ2Vδ2 T Cells

Yang¹,

Shen²,

Gong³

et al. 2020

Preprint

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Background: Anti-cancer immunotherapy based on the adoptive transfer of Vγ2Vδ2 T cells has benefited to some patients in clinical trials, but the overall responses are inconsistent. Therefore, new strategies are urgently needed to improve the current therapy.Methods: In this study, a designed bispecific antibody Y111, which binds to both CD3 and PD-L1, is applied to optimally potentiate Vγ2Vδ2 T cell-based killing of cancer cells. The binding activities of Y111 was determined by Flow cytometry. CFSE/PI-based flow cytometry was applied to check the re-directed killing ability induced by Y111 in the condition of using T cell subsets, or expanded- and purified- Vγ2Vδ2 T cells as effector cells. Moreover, expanded- and purified- Vγ2Vδ2 T cells were co-cultured with tumor cells in the presence/absence of Y111 to assess the activation, degranulation, and cytokine production by intracellular cytokine staining, and CBA method. Finally, NPG-based subcutaneous tumor mouse models were used to check the in vivo therapeutic efficacy of the combination of transfused Vγ2Vδ2 T cells and Y111.Results: Due to its binding activities, Y111 apparently prompts fresh αβ-mediated lysis of tumor cell line H358 cells, but spare the effect on the fresh enriched Vγ2Vδ2 T cells from the same donors. However, Y111 increases cytotoxicity of expanded and purified Vγ2Vδ2 T cells against various NSCLC-derived tumor cell lines in a tumor cell dependent fashion. Y111 also prompted the releases of granzyme B, IFNγ and TNFα. Supporting to these observations in vitro, a combination of adoptive transferring Vγ2Vδ2 T cell and Y111 into the tumor-bearing NPG mice inhibited the growth of the established tumors in the mice.Conclusions: Taken together, our data suggest clinical potential for adoptive transferring the bispecific antibody-armored Vγ2Vδ2 T cells to treat solid tumors, such as NSCLC.

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Impairment of Wnt/β-catenin signaling in blood cells of patients with severe cavitary pulmonary tuberculosis

Cited by 11 publications

References 26 publications

The Role of β-Catenin in Th1 Immune Response against Tuberculosis and Profiles of Expression in Patients with Pulmonary Tuberculosis

The Role of β-Catenin in Th1 Immune Response against Tuberculosis and Profiles of Expression in Patients with Pulmonary Tuberculosis

The crucial roles of Th17-related cytokines/signal pathways in M. tuberculosis infection

Bi-specific Antibody Y111, Targeting PD-L1 and CD3 Considerably Enhances the Therapeutic Efficacy of Adoptive Transferred Vγ2Vδ2 T Cells

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