Dendritic cells in autoimmunity, infections, and cancer

Quintana, Francisco J.

doi:10.1007/s00281-016-0618-5

Cited by 5 publications

(3 citation statements)

References 10 publications

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“…Therefore, DCs have become a bridge between innate and adaptive immunity, playing a crucial role in regulating immune responses (Mellman, 2013). A recent study verified that DCs were involved in the processes of a variety of diseases, such as infections, tumors, transplant rejection, and autoimmune diseases (Quintana, 2017). DC immune activation and tolerance have been widely applied in disease therapeutics (Audiger, Rahman, Yun, Tarbell, & Lesage, 2017).…”

Section: Introductionmentioning

confidence: 99%

Indirubin regulates T cell differentiation by promoting αVβ8 expression in bone marrow‐derived dendritic cells to alleviate inflammatory bowel disease

Tao

Peng

et al. 2022

Phytotherapy Research

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Inflammatory bowel disease is a disease that can invade the whole digestive tract and is accompanied by immune abnormalities. Immune dysfunction involving dendritic cells (DCs) and T cells is recognized as a key factor in diseases. Indirubin (IDRB) exerts antiinflammatory effects and can help in treating immune diseases. This study aimed to isolate bone marrow‐derived dendritic cells (BMDCs) using lipopolysaccharide (LPS) to obtain mature DCs (mDCs). The expression of CD80, CD86, CD40, and MHC‐II was detected using flow cytometry after treatment with IDRB. αVβ8 siRNA was used to knock down αVβ8 in mDCs, and the expression of CD80, CD86, CD40, and MHC‐II was detected. Meanwhile, DCs were co‐cultured with T cells. Then, T cell differentiation was detected using flow cytometry, and the cytokine levels were detected using enzyme‐linked immunosorbent assay. The animal model of dextran sulfate sodium (DSS)‐induced inflammatory bowel disease was established in mice. After intervention with IDRB and αVβ8 shRNA, the intestinal tissues were evaluated using H&E staining, disease activity index (DAI) score, and histological damage index, and the corresponding factors and cytokines to regulatory T cells (Treg) and Th17 were measured. The results showed that αVβ8 was expressed in immature DCs and mDCs. CD80, CD86, CD40, and MHC‐II expression decreased after IDRB treatment in mDCs. Meanwhile, the expression of TNF‐α and TGF‐β also decreased after IDRB treatment. The effect of IDRB on the expression of CD80, CD86, CD40, MHC‐II, TNF‐α, and TGF‐β in mDCs was reversed by αVβ8 siRNA. The Treg differentiation increased after IDRB treatment, while the differentiation of Th17 cells was inhibited. This effect of IDRB was reversed by mDCs after treatment with αVβ8 siRNA. In vivo experiments showed that IDRB alleviated the symptoms of inflammatory bowel disease in animals. Enteritis significantly reduced, and the effect of IDRB was reversed by αVβ8 shRNA. The results suggested that IDRB regulated the differentiation of T cells by mediating the maturation of BMDCs through αVβ8. This study confirmed the therapeutic effect of IDRB in inflammatory bowel disease and suggested that IDRB might serve as a potential drug.

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Section: Introductionmentioning

confidence: 99%

Indirubin regulates T cell differentiation by promoting αVβ8 expression in bone marrow‐derived dendritic cells to alleviate inflammatory bowel disease

Tao

Peng

et al. 2022

Phytotherapy Research

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“…Dendritic cells represent the most important APCs, linking innate and adaptive immune responses, with the capacity of controlling both immunity and tolerance (19). Vitamin D 3 can induce potent tolerogenic characteristics in DCs by strongly up-regulating various surface inhibitory molecules and increasing their capacity to produce IL-10 upon activation (20).…”

Section: Introductionmentioning

confidence: 99%

Synergistic Effects of Interferon-γ and Vitamin D3 Signaling in Induction of ILT-3highPDL-1high Tolerogenic Dendritic Cells

Švajger

Rožman

2019

Front. Immunol.

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In the past, interferon (IFN)-γ and vitamin D3 (vit D3) have both been associated with induction of tolerogenic characteristics in human dendritic cells (DCs). Although there are only a few reports on interdependency of their actions, the interplay between IFN-γ and vit D3 has been clearly demonstrated in certain aspects of immune reactivity. Since both agents have been associated with regulation of immune responses, we set out to examine their functional and mechanistic interactions in context of principal regulators of immunity, the DCs. Combined treatment with vit D3 and IFN-γ caused an extensive expression of immunoglobulin-like transcript (ILT)-3 and programmed death ligand (PDL)-1 on γ/D3DCs, significantly greater than that caused by vit D3 alone. Such γ/D3DCs retained all general DC characteristics. After CD40 ligand-induced activation, they produced increased amounts of IL-10 with almost absent production of IL-12p70. On the other hand, the co-stimulatory potential of γ/D3DCs was weak, with cells possessing the capacity to inhibit CD4+ T cell, CD8+ T cell, as well as memory T cell responses. Naive CD4+ T cells stimulated with γ/D3DCs produced increased amounts of IL-10 with concomitantly low IFN-γ production, upon T cell receptor activation. Additionally, γ/D3DCs completely inhibited granzyme B expression by CD8+ T cells. The percentage of FoxP3-positive cells in co-cultures with naive CD4+ T cells was significantly higher where γ/D3DCs were used as stimulators compared to DCs treated with vit D3 alone and it could be partially reversed by PDL-1 blockade. Interestingly, γ/D3DCs were inefficient at suppressing mDC-induced CD4+ T cell proliferation, but were twice as effective as D3DCs at suppressing mDC-induced CD8+ T cell proliferation. Blockade of indoleamine-2,3-dioxygenase did not reduce the tolerogenic phenotype induced by IFN-γ and vit D3 treatment. Examination of signaling pathways activation revealed a tendency toward increased ERK and Akt phosphorylation in γ/D3DCs. Inhibition of MEK/ERK and PI3K/mTOR pathways significantly reduced the expression of ILT-3 and PDL-1 on γ/D3DCs. In summary, we present the first evidence for existing synergy between IFN-γ and vit D3 in shaping a unique tolerogenic DC activation state.

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“…Mature DCs play a powerful antigen presenting role to activate T cells and to secrete a variety of cytokines that affect T helper (Th) cell differentiation. Thus, DCs are the key to the pathogenesis of many autoimmune diseases and may also be a main therapeutic target for these diseases [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Study on the Inhibitory Effects of Ephedra Aconite Asarum Decoction on LPS‐Induced Dendritic Cells

et al. 2017

Evidence-Based Complementary and Alternative Medicine

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Dendritic cells (DCs) can secrete cytokines stimulated by lipopolysaccharide (LPS), which leads to not just acute inflammatory responses but also Th1 polarization. Furtherly, chronic inflammation or autoimmune diseases could be triggered. As a classic Traditional Chinese Medicine formula, Ephedra Aconite Asarum Decoction with the main ingredients of ephedrine and hypaconitine can show effect on anti-inflammation and immunoregulation. But it remains unclear whether Ephedra Aconite Asarum Decoction controls DCs. In this study, we investigated the effects of Ephedra Aconite Asarum Decoction on LPS-induced bone marrow-derived DCs (BMDCs) in vitro. We found that Ephedra Aconite Asarum Decoction lowered surface costimulators on DCs and reduced the expression of Th1 type cytokines. Yet it is slightly beneficial for shifting to Th2. Our work reveals that the Ephedra Aconite Asarum Decoction can regulate Th1 inflammation through intervening DCs.

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Dendritic cells in autoimmunity, infections, and cancer

Cited by 5 publications

References 10 publications

Indirubin regulates T cell differentiation by promoting αVβ8 expression in bone marrow‐derived dendritic cells to alleviate inflammatory bowel disease

Indirubin regulates T cell differentiation by promoting αVβ8 expression in bone marrow‐derived dendritic cells to alleviate inflammatory bowel disease

Synergistic Effects of Interferon-γ and Vitamin D3 Signaling in Induction of ILT-3highPDL-1high Tolerogenic Dendritic Cells

Study on the Inhibitory Effects of Ephedra Aconite Asarum Decoction on LPS‐Induced Dendritic Cells

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