Impact of immune checkpoint molecules on FoxP3+ Treg cells and related cytokines in patients with acute and chronic brucellosis

Sun, Huali; Du, Xiu‐Fang; Tang, Yuling; Li, Guoqiang; Yang, Siyuan; Wang, Ling-Hang; Li, Xingwang; Ma, Chang–Jin; Jiang, Rongmeng

doi:10.1186/s12879-021-06730-3

Cited by 8 publications

(9 citation statements)

References 45 publications

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“…Finally, it is described that immune checkpoints may mediate the immunomodulatory functions of Tregs during the development and progression of several infectious diseases ( Sun et al, 2021 ). Noteworthy, FOXP3, the transcription factor that masters the differentiation and function of Tregs, was found to be upregulated at mRNA and protein level in the lung and tracheobronchial lymph node from Lena and 3249-infected piglets in a parallel studio, and it was associated with the constraint and recovery of lung injury during acute PRRSV infection ( Sánchez-Carvajal et al, 2020 ; Ruedas-Torres et al, 2021a ).…”

Section: Discussionmentioning

confidence: 99%

PRRSV-1 induced lung lesion is associated with an imbalance between costimulatory and coinhibitory immune checkpoints

et al. 2023

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Porcine reproductive and respiratory syndrome virus (PRRSV) induces a dysregulation on the innate and adaptive immune responses. T-cell activation requires a proper interaction and precise balance between costimulatory and coinhibitory molecules, commonly known as immune checkpoints. This study aims to evaluate the expression of immune checkpoints in lung and tracheobronchial lymph node from piglets infected with two PRRSV-1 strains of different virulence during the early stage of infection. Seventy 4-week-old piglets were grouped into three experimental groups: (i) control, (ii) 3249-infected group (low virulent strain), and (iii) Lena-infected group (virulent strain) and were euthanized at 1, 3, 6, 8, and 13 days post-infection (dpi). Lung and tracheobronchial lymph node were collected to evaluate histopathological findings, PRRSV viral load and mRNA expression of costimulatory (CD28, CD226, TNFRSF9, SELL, ICOS, and CD40) and coinhibitory (CTLA4, TIGIT, PD1/PDL1, TIM3, LAG3, and IDO1) molecules through RT-qPCR. Our findings highlight a mild increase of costimulatory molecules together with an earlier and stronger up-regulation of coinhibitory molecules in both organs from PRRSV-1-infected animals, especially in the lung from virulent Lena-infected animals. The simultaneous expression of coinhibitory immune checkpoints could work in synergy to control and limit the inflammation-induced tissue damage. Further studies should be addressed to determine the role of these molecules in later stages of PRRSV infection.

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Section: Discussionmentioning

confidence: 99%

PRRSV-1 induced lung lesion is associated with an imbalance between costimulatory and coinhibitory immune checkpoints

et al. 2023

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“… 29 Among our patients, the increase in the level of the anti-inflammatory cytokine IL-10 was observed in acute infection, which indicated that IL-10 was induced to ensure homeostasis in patients during infection; the finding is consistent with those of previous studies. 29 , 39 , 40 Xavier et al reported that a lack of IL-10 production by T cells resulted in an increased function to control B. abortus infection while inducing elevated expression of pro-inflammatory cytokines in a murine model. 13 Moreover, its ability to resist further pro-inflammatory responses was supported by reduced levels of pro-inflammatory cytokines during our patients’ treatment.…”

Section: Discussionmentioning

confidence: 99%

Serum Levels of Seven General Cytokines in Acute Brucellosis Before and After Treatment

Tang¹,

Ma²,

Sun³

et al. 2021

IDR

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Purpose Human brucellosis is the most common bacterial zoonosis globally that poses a severe health threat. Despite the availability of antibiotic therapy for human brucellosis, its tendencies of chronicity and persistence may lead to severe debilitating and disabling conditions in patients. Comprehensive understanding of the immune response in brucellosis will be helpful in improving the treatment strategies. In this study, we measured serum levels of T helper cell type 1 (Th1), Th2, and Th17 cytokines in patients with acute brucellosis before and after treatment. Patients and Methods Overall, 30 patients with acute brucellosis from the Beijing Di Tan Hospital and 26 healthy controls were enrolled in this study. All the patients received a 6-week therapy regimen comprising ceftriaxone, doxycycline, and rifampicin. Serum samples were collected from patients with acute Brucella infection and healthy controls before and after treatment. Serum seven cytokine levels of Th1 (IL-2, IFN-γ, and TNF-α), Th2 (IL-4, IL-6, IL-10), and Th17 (IL-17A) were measured using cytometric bead array. Results In patients with acute infection, the IL-2, IFN-γ, and IL-10 levels were significantly increased compared with those in healthy controls (P < 0.001). After treatment, IL-2, IFN-γ, and IL-10 levels significantly decreased (P < 0.05) and the TNF-α level significantly increased compared with the corresponding baseline levels and those in healthy controls (P < 0.05). Furthermore, the IFN-γ, IL-4, and IL-10 levels were higher in patients after treatment than in healthy controls (P < 0.05). IL-2 and IL-6 levels exhibited a positive correlation with the C-reactive protein (CRP) level in acute brucellosis (P < 0.05). Conclusion Levels of most serum Th1 and Th2 cytokines were simultaneously increased in acute infection, followed by reduction in the corresponding cytokine levels and residual cytokine response during treatment. This residual immune response could represent a therapeutic opportunity that may improve the long-term clinical outcomes in patients with acute brucellosis after treatment.

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“…Blocking CTLA-4 significantly eliminated the inhibitory effect of Foxp3 + Tregs on the PPD-specific T cell proliferation response ( 152 ). Therefore, CTLA-4 is a promising new target for immunotherapy for active tuberculosis ( 153 ).…”

Section: Co-stimulatory Moleculesmentioning

confidence: 99%

Regulation of Treg cells by cytokine signaling and co-stimulatory molecules

Zong,

Deng,

Chong

2024

Front. Immunol.

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CD4+CD25+Foxp3+ regulatory T cells (Tregs), a vital component of the immune system, are responsible for maintaining immune homeostasis and preventing excessive immune responses. This review explores the signaling pathways of the cytokines that regulate Treg cells, including transforming growth factor beta (TGF-β), interleukin (IL)-2, IL-10, and IL-35, which foster the differentiation and enhance the immunosuppressive capabilities of Tregs. It also examines how, conversely, signals mediated by IL-6 and tumor necrosis factor -alpha (TNF-α) can undermine Treg suppressive functions or even drive their reprogramming into effector T cells. The B7 family comprises indispensable co-stimulators for T cell activation. Among its members, this review focuses on the capacity of CTLA-4 and PD-1 to regulate the differentiation, function, and survival of Tregs. As Tregs play an essential role in maintaining immune homeostasis, their dysfunction contributes to the pathogenesis of autoimmune diseases. This review delves into the potential of employing Treg-based immunotherapy for the treatment of autoimmune diseases, transplant rejection, and cancer. By shedding light on these topics, this article aims to enhance our understanding of the regulation of Tregs by cytokines and their therapeutic potential for various pathological conditions.

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Impact of immune checkpoint molecules on FoxP3+ Treg cells and related cytokines in patients with acute and chronic brucellosis

Cited by 8 publications

References 45 publications

PRRSV-1 induced lung lesion is associated with an imbalance between costimulatory and coinhibitory immune checkpoints

PRRSV-1 induced lung lesion is associated with an imbalance between costimulatory and coinhibitory immune checkpoints

Serum Levels of Seven General Cytokines in Acute Brucellosis Before and After Treatment

Regulation of Treg cells by cytokine signaling and co-stimulatory molecules

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