Cross Talk Between Natural Killer T and Dendritic Cells and Its Impact on T Cell Responses in Infections

Zhao, Lei; Yang, Xi

doi:10.3389/fimmu.2022.837767

Cited by 14 publications

(8 citation statements)

References 78 publications

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“…A large number of DAMPs can activate the innate immune system by binding to PRRs on the surface of a variety of immune cells, mediating downstream inflammatory pathways to generate a range of cytokines and chemokines. As a conserved T cell subline, NKT cells can be activated and then rapidly produce cytokines in response to antigen presentation by DCs 19 , 20 , while CXCL6-expressing DCs can bind to NKTs expressing the chemokine receptor CXCR6 to promote NKT cell activation/maturation 21 . Activated NKT cells promote CD4 + T cell differentiation and act on Kupffer cells by further generating IL-17, inducing downstream pro-inflammatory mediator expression 22 – 25 , and generating large amounts of ROS, which can further act on HSEC and hepatocytes to promote programmed cellular death or necrosis, expanding the inflammatory cascade 26 (Fig.…”

Section: Discussionmentioning

confidence: 99%

Analysis and experimental validation of IL-17 pathway and key genes as central roles associated with inflammation in hepatic ischemia–reperfusion injury

Tan,

Lu,

Chen

et al. 2024

Sci Rep

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Hepatic ischemia–reperfusion injury (HIRI) elicits an immune-inflammatory response that may result in hepatocyte necrosis and apoptosis, ultimately culminating in postoperative hepatic dysfunction and hepatic failure. The precise mechanisms governing the pathophysiology of HIRI remain incompletely understood, necessitating further investigation into key molecules and pathways implicated in disease progression to guide drug discovery and potential therapeutic interventions. Gene microarray data was downloaded from the GEO expression profile database. Integrated bioinformatic analyses were performed to identify HIRI signature genes, which were subsequently validated for expression levels and diagnostic efficacy. Finally, the gene expression was verified in an experimental HIRI model and the effect of anti-IL17A antibody intervention in three time points (including pre-ischemic, post-ischemic, and at 1 h of reperfusion) on HIRI and the expression of these genes was investigated. Bioinformatic analyses of the screened characterized genes revealed that inflammation, immune response, and cell death modulation were significantly associated with HIRI pathophysiology. CCL2, BTG2, GADD45A, FOS, CXCL10, TNFRSF12A, and IL-17 pathway were identified as key components involved in the HIRI. Serum and liver IL-17A expression were significantly upregulated during the initial phase of HIRI. Pretreatment with anti-IL-17A antibody effectively alleviated the damage of liver tissue, suppressed inflammatory factors, and serum transaminase levels, and downregulated the mRNA expression of CCL2, GADD45A, FOS, CXCL10, and TNFRSF12A. Injection of anti-IL17A antibody after ischemia and at 1 h of reperfusion failed to demonstrate anti-inflammatory and attenuating HIRI benefits relative to earlier intervention. Our study reveals that the IL-17 pathway and related genes may be involved in the proinflammatory mechanism of HIRI, which may provide a new perspective and theoretical basis for the prevention and treatment of HIRI.

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Section: Discussionmentioning

confidence: 99%

Analysis and experimental validation of IL-17 pathway and key genes as central roles associated with inflammation in hepatic ischemia–reperfusion injury

Tan,

Lu,

Chen

et al. 2024

Sci Rep

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“…Our analysis not only demonstrated an increased percentage of dendritic cells but, importantly, a reduced proportion of immunosuppressive iNOS-producing dendritic cells within the tumor environment of metformin-treated mice ( Figure 5 I,J). These findings imply that metformin’s modulatory effects on the immune system may involve intricate interactions between NKT cells and dendritic cells, thus potentially altering T cell phenotypes to bolster anticancer immunity [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

Harnessing Metformin’s Immunomodulatory Effects on Immune Cells to Combat Breast Cancer

Petrovic,

Jovanovic,

Stojanovic

et al. 2024

IJMS

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Metformin, a medication known for its anti-glycemic properties, also demonstrates potent immune system activation. In our study, using a 4T1 breast cancer model in BALB/C WT mice, we examined metformin’s impact on the functional phenotype of multiple immune cells, with a specific emphasis on natural killer T (NKT) cells due to their understudied role in this context. Metformin administration delayed the appearance and growth of carcinoma. Furthermore, metformin increased the percentage of IFN-γ+ NKT cells, and enhanced CD107a expression, as measured by MFI, while decreasing PD-1+, FoxP3+, and IL-10+ NKT cells in spleens of metformin-treated mice. In primary tumors, metformin increased the percentage of NKp46+ NKT cells and increased FasL expression, while lowering the percentages of FoxP3+, PD-1+, and IL-10-producing NKT cells and KLRG1 expression. Activation markers increased, and immunosuppressive markers declined in T cells from both the spleen and tumors. Furthermore, metformin decreased IL-10+ and FoxP3+ Tregs, along with Gr-1+ myeloid-derived suppressor cells (MDSCs) in spleens, and in tumor tissue, it decreased IL-10+ and FoxP3+ Tregs, Gr-1+, NF-κB+, and iNOS+ MDSCs, and iNOS+ dendritic cells (DCs), while increasing the DCs quantity. Additionally, increased expression levels of MIP1a, STAT4, and NFAT in splenocytes were found. These comprehensive findings illustrate metformin’s broad immunomodulatory impact across a variety of immune cells, including stimulating NKT cells and T cells, while inhibiting Tregs and MDSCs. This dynamic modulation may potentiate its use in cancer immunotherapy, highlighting its potential to modulate the tumor microenvironment across a spectrum of immune cell types.

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“…Dendritic cells (DCs) are an important cell type in the immune system, responsible for antigen presentation and promoting immune responses by activating specific T cells (15). Dendritic cells possess highly differentiated cell surface molecules, including HLA-DR, CD86, and CD54, which play important roles in the process of dendritic cell activation of T cells (21)(22)(23)(24)(25). This study found that patients with ACLF exhibited significantly reduced expression of surface markers HLA-DR, CD86, and CD54 compared to patients with CHB or healthy individuals.…”

Section: Discussionmentioning

confidence: 99%

Comparative analysis of monocyte-derived dendritic cell phenotype and T cell stimulatory function in patients with acute-on-chronic liver failure with different clinical parameters

Wu,

Shi,

Zhang

et al. 2023

Front. Immunol.

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BackgroundAcute-on-Chronic Liver Failure (ACLF) patients experience systemic inflammation as well as immune dysfunction and exhaustion. The phenotype and functionality of monocyte-derived dendritic cells in ACLF patients with different clinical parameters have not been elucidated.MethodsThis study included 37 cases of ACLF, 20 cases of Chronic Hepatitis B (CHB) patients, and 12 healthy controls. Demographic and laboratory parameters were collected from the enrolled patients. Peripheral blood samples were obtained from the participants. Monocyte-derived dendritic cells were induced and cultured, followed by co-culturing with T cells from the patients. Cell surface markers and intracellular markers were analyzed using flow cytometry. The relationship between these markers and clinical parameters was compared.ResultsOur study found that ACLF patients had lower expression levels of HLA-DR, CD86, and CD54 on monocyte-derived dendritic cells compared to both CHB patients and healthy controls. IL-4, GM-CSF, and alcohol were found to promote the expression of HLA-DR, CD86, and CD54 on monocyte-derived dendritic cells. In ACLF patients, higher levels of procalcitonin (PCT), lower levels of albumin, decreased prothrombin activity and deceased patients were associated with lower expression of HLA-DR, CD86, and CD54 on monocyte-derived dendritic cells. Peripheral blood mononuclear cells (PBMCs), after removing adherent cells, were co-cultured with monocyte-derived DC. Our study revealed that patients with infection and low albumin levels exhibited a decreased proportion of T cell subsets within PBMCs. Additionally, these patients’ T cells showed lower levels of Ki-67 and interferon-gamma (IFN-γ) production.ConclusionACLF patients exhibit varying clinical states, with differences in the phenotype and the ability of monocyte-derived dendritic cells to stimulate T cells. Alcohol can stimulate the maturation of monocyte-derived dendritic cells.

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Cross Talk Between Natural Killer T and Dendritic Cells and Its Impact on T Cell Responses in Infections

Cited by 14 publications

References 78 publications

Analysis and experimental validation of IL-17 pathway and key genes as central roles associated with inflammation in hepatic ischemia–reperfusion injury

Analysis and experimental validation of IL-17 pathway and key genes as central roles associated with inflammation in hepatic ischemia–reperfusion injury

Harnessing Metformin’s Immunomodulatory Effects on Immune Cells to Combat Breast Cancer

Comparative analysis of monocyte-derived dendritic cell phenotype and T cell stimulatory function in patients with acute-on-chronic liver failure with different clinical parameters

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