Dendritic cells trigger imbalance of Th1/Th2 cells in silica dust exposure rat model <i>via</i> MHC-II, CD80, CD86 and IL-12

Bao, Lei; Hao, Changfu; Liu, Suna; Zhang, Lin; Wang, Juan; Wang, Di; Li, Yiping; Yao, Wu

doi:10.1039/c8ra03970d

Cited by 15 publications

(6 citation statements)

References 48 publications

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“…Recent experimental and clinical studies suggest that persistent Th1/Th2 imbalance in the lung represents a possible additional mechanism involved in pulmonary fibrosis progression (15). Our recent investigations have demonstrated that DCs accumulated in lung tissues of rats exposed to silica dust and regulated the polarization of Th1/Th2 cells (40). In this study, the results showed that indirect silica exposure induces a blockade of DC maturation by reducing cell surface expression of these molecules, leading us to consider whether silica stimulation can alter the capacity of DCs to stimulate T cells.…”

Section: Discussionmentioning

confidence: 99%

Silica Particles Mediate Phenotypic and Functional Alteration of Dendritic Cells and Induce Th2 Cell Polarization

et al. 2019

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During silicosis, immune cells, including macrophages, T cells, B cells, and NK cells, participate in fibrosis development through alteration of the immune status. Dendritic cells (DCs) are professional antigen-presenting cells (APCs) with a key role in initiating immune responses and sustaining immune tolerance to maintain homeostasis. The relative contribution of DCs to silicosis progression is not well-documented. In the current study, we investigated the phenotypic and functional alterations of peripheral blood mononuclear cell (PBMC)-derived DCs of Sprague–Dawley (SD) rat during immune responses to silica exposure. We established models for direct and indirect exposure of DCs to silica by either treating DCs with silica or coculturing them with alveolar macrophages (AMs) treated with silica, respectively. The functional activity of DCs was analyzed by measuring their expression of costimulatory molecules, fluorescent microparticle uptake, cytokine production, and ability to mediate T cell polarization in vitro . In vivo , we demonstrated that silica could induce DC migration in response to silica exposure. Our results show that cytokine production by DCs was increased in response to direct silica direct exposure, while indirect silica exposure led to reduced cytokine levels. Moreover, the phagocytic capacity of DCs increased in cocultures after silica exposure. Gene and protein expression analyses showed that silica exposure altered the expression levels of Toll-like receptor pathway proteins and inflammatory factors. DC surface expression of the costimulatory molecules, CD80, CD86, and major histocompatibility complex, was inhibited by exposure to silica, which mediated a Th2-polarizing response in vitro . In rats, silica exposure induced migration of DCs from the peripheral blood into the alveoli. These results demonstrate that direct and indirect exposure to silica particles alter the phenotype and function of DCs, thereby regulating immune responses. Such changes may contribute to the development of silicosis by altering DC phenotype, function, and migration and by influencing the balance between Th1 and Th2 cells.

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Section: Discussionmentioning

confidence: 99%

Silica Particles Mediate Phenotypic and Functional Alteration of Dendritic Cells and Induce Th2 Cell Polarization

et al. 2019

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“…Knockout of STAT6 in mice appeared to block Th2 polarization induced by MWCNTs as shown by loss of induction of IL-5 in STAT6 knockout mice compared to wild type (86). Silica also increased the number of Th2 cells in fibrotic lung tissues of rats (79). Patients with silicosis had elevated level of Th2 cells (74).…”

Section: Th2smentioning

confidence: 96%

“…Th1 and ILC1 cells secrete IFN-γ and TNF-α that stimulate the polarization of macrophages toward an M1 phenotype, a major cellular event in the initiation and amplification of type 1 inflammation. A recent study reveals that exposure of rats to silica by intra-tracheal instillation increased the number of Th1 cells and the levels of IFN-γ and IL-12 in the lung, which were likely to be stimulated by increased recruitment of DCs in the early inflammatory phase of the pulmonary response (79). In a separate study, exposure to amorphous silica nanoparticles enhanced the polarization of Th1 lymphocytes and the production of IFN-γ in ovalbumin (OVA)sensitized mice (67).…”

Section: Polarization Of Type 1 Immune Cellsmentioning

confidence: 99%

“…Induction of the genes and proteins occurred between the 1st and the 2nd week with a peak at day 7 upon a single exposure (69). Exposure of rats to silica induced the expression of IL-4 during the fibrotic stage of the pulmonary response (79). Patients with asbestosis have elevated expression of IL-10 in their AMs (66), whereas patients with silicosis showed increased levels of IL-10, IL-4, IL-5, and IL13 in their serum (74).…”

Section: Type 2 Cytokinesmentioning

confidence: 99%

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Polarization of Immune Cells in the Pathologic Response to Inhaled Particulates

2020

Front. Immunol.

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“…Detection of Th cells in the peripheral blood of rats was performed according to the literature (Lei et al, 2018).…”

Section: Flow Cytometric Analysis Of Th Cellsmentioning

confidence: 99%

High-Dose Cyclophosphamide Administration Orchestrates Phenotypic and Functional Alterations of Immature Dendritic Cells and Regulates Th Cell Polarization

et al. 2020

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High-dose cyclophosphamide (CTX) inhibits the immune response. Dendritic cells (DCs) are professional antigen presenting cells (APCs) with a crucial role in initiating immune responses and sustaining immune tolerance. The relative contribution of DCs to immunosuppression induced by high-dose CTX is not well-documented. In this study, we employed the CTX-induced immunosuppressive rat model to examine alterations in DCs. We generated and cultured monocyte-derived immature DCs (imDCs) in vitro and explored their capacity of antigen uptake, T cell priming, cytokine production, and surface marker expression following high-dose CTX. Subsequently, we co-cultured CTX-treated imDCs with Th cells to determine Th cell polarization, and further explored the Toll-like receptor/Myeloid differentiation primary response 88/Mitogen-activated protein kinase (TLR/MyD88/MAPK) pathway. Our results show reduced cell number and surface maker alterations in splenic CD103 + DCs of CTX-treated immunosuppressed rats. In vitro, highdose CTX weakened the antigen uptake capacity and enhanced the T cell priming capacity of imDCs, in addition to triggering imDC surface marker alterations. TLR, MyD88, and MAPK expression levels, involved in mediating Th cell polarization, were also significantly elevated. Our collective findings indicate that high-dose CTX administration potentiates phenotypic and functional alterations of imDC. Such changes may contribute to the regulation of Th polarization.

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Dendritic cells trigger imbalance of Th1/Th2 cells in silica dust exposure rat model via MHC-II, CD80, CD86 and IL-12

Cited by 15 publications

References 48 publications

Silica Particles Mediate Phenotypic and Functional Alteration of Dendritic Cells and Induce Th2 Cell Polarization

Silica Particles Mediate Phenotypic and Functional Alteration of Dendritic Cells and Induce Th2 Cell Polarization

Polarization of Immune Cells in the Pathologic Response to Inhaled Particulates

High-Dose Cyclophosphamide Administration Orchestrates Phenotypic and Functional Alterations of Immature Dendritic Cells and Regulates Th Cell Polarization

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