The Vitamin D3 analogue calcipotriol suppresses CpG-activated TLR9-MyD88 signalling in murine plasmacytoid dendritic cells

Suzuki, Takahiro; Sakabe, Jun‐ichi; Funakoshi, Akihiro; Tokura, Y.

doi:10.1111/ced.13397

Cited by 7 publications

(6 citation statements)

References 9 publications

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“…Intriguingly, this expression was found decreased in D 3 -MDMs. This data is in line with other studies in which VitD3 was shown to decrease TLR9 expression in HeLa cells infected with Herpes simplex virus-1 [47], in monocytes [48], in murine plasmacytoid DCs [49], and in DENV-2 infected Mo-DCs [50]. We also found that VitD3 reduced the production of ROS at 2 hpi in D 3 -MDMs after infection with DENV-2.…”

Section: Plos Neglected Tropical Diseasessupporting

confidence: 93%

Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2

et al. 2021

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A dysregulated or exacerbated inflammatory response is thought to be the key driver of the pathogenesis of severe disease caused by the mosquito-borne dengue virus (DENV). Compounds that restrict virus replication and modulate the inflammatory response could thus serve as promising therapeutics mitigating the disease pathogenesis. We and others have previously shown that macrophages, which are important cellular targets for DENV replication, differentiated in the presence of bioactive vitamin D (VitD3) are less permissive to viral replication, and produce lower levels of pro-inflammatory cytokines. Therefore, we here evaluated the extent and kinetics of innate immune responses of DENV-2 infected monocytes differentiated into macrophages in the presence (D3-MDMs) or absence of VitD3 (MDMs). We found that D3-MDMs expressed lower levels of RIG I, Toll-like receptor (TLR)3, and TLR7, as well as higher levels of SOCS-1 in response to DENV-2 infection. D3-MDMs produced lower levels of reactive oxygen species, related to a lower expression of TLR9. Moreover, although VitD3 treatment did not modulate either the expression of IFN-α or IFN-β, higher expression of protein kinase R (PKR) and 2′-5′-oligoadenylate synthetase 1 (OAS1) mRNA were found in D3-MDMs. Importantly, the observed effects were independent of reduced infection, highlighting the intrinsic differences between D3-MDMs and MDMs. Taken together, our results suggest that differentiation of MDMs in the presence of VitD3 modulates innate immunity in responses to DENV-2 infection.

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Section: Plos Neglected Tropical Diseasessupporting

confidence: 93%

Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2

et al. 2021

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“…Conventional psoriasis therapies, including topical applications of vitamin D analogs or vitamin A analogs, have also been shown to exert their anti-inflammatory effects by modulating TLR function. Vitamin D3 downregulates the expression of TLR2, TLR4, and TLR9 and suppresses TLR9-mediated cytokine production in human monocytes [115], and the vitamin D analog calcipotriol attenuates CpG-mediated elevation of TLR9 and MyD88 expression in pDCs [116]. Retinoids, namely, vitamin A and its metabolites, have been used to treat psoriasis since the 1980s.…”

Section: Tlr-targeted Therapiesmentioning

confidence: 99%

The Role of Toll-Like Receptors in Skin Host Defense, Psoriasis, and Atopic Dermatitis

Sun

Liu

Zhang

2019

Journal of Immunology Research

119

105

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As the key defense molecules originally identified in Drosophila, Toll-like receptor (TLR) superfamily members play a fundamental role in detecting invading pathogens or damage and initiating the innate immune system of mammalian cells. The skin, the largest organ of the human body, protects the human body by providing a critical physical and immunological active multilayered barrier against invading pathogens and environmental factors. At the first line of defense, the skin is constantly exposed to pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), and TLRs, expressed in a cell type-specific manner by various skin cells, serve as key molecules to recognize PAMPs and DAMPs and to initiate downstream innate immune host responses. While TLR-initiated inflammatory responses are necessary for pathogen clearance and tissue repair, aberrant activation of TLRs will exaggerate T cell-mediated autoimmune activation, leading to unwanted inflammation, and the development of several skin diseases, including psoriasis, atopic dermatitis, systemic lupus erythematosus, diabetic foot ulcers, fibrotic skin diseases, and skin cancers. Together, TLRs are at the interface between innate immunity and adaptive immunity. In this review, we will describe current understanding of the role of TLRs in skin defense and in the pathogenesis of psoriasis and atopic dermatitis, and we will also discuss the development and therapeutic effect of TLR-targeted therapies.

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“…TLR1, TLR2, TLR4, TLR5, and TLR6 are located on the cell surface but TLR3, TLR7, TLR8, and TLR9 are within endosomes [ 40 ]. Furthermore, TLR2 recognizes bacterial lipoproteins, TLR4 recognizes lipopolysaccharides (LPS), and TLR9 recognizes CpG-containing DNA (CpG-ODN) [ 41 , 42 ].…”

Section: Toll-like Receptormentioning

confidence: 99%

The Cancer Prevention, Anti-Inflammatory and Anti-Oxidation of Bioactive Phytochemicals Targeting the TLR4 Signaling Pathway

Chen

Kao

Liu

2018

IJMS

253

143

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Toll-like receptors (TLRs) are a well-known family of pattern recognition receptors that play an important role in a host immune system. TLR triggering leads to the induction of pro-inflammatory cytokines and chemokines, driving the activation of both innate and adaptive immunity. Recently, an increasing number studies have shown the link between TLRs and cancer. Among them, the toll-like receptor 4 (TLR4) signaling pathway is associated with inflammatory response and cancer progression. Dietary phytochemicals are potential modulators of immunological status with various pharmacological properties including anti-cancer, anti-oxidant and anti-inflammatory. Curcumin, 6-gingerol, 6-shogaol, 1-dehydro-10-gingerdione, epigallocatechin gallate (EGCG), luteolin, quercetin, resveratrol, caffeic acid phenethyl ester, xanthohumol, genistein, berberine, and sulforaphane can inhibit TLR4 activation. The aim of the present review is to describe the role of the TLR4 signaling pathway between inflammatory response and cancer progression. We further introduce bioactive phytochemicals with potential anti-inflammation and chemoprevention by inhibiting TLR activation.

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The Vitamin D3 analogue calcipotriol suppresses CpG-activated TLR9-MyD88 signalling in murine plasmacytoid dendritic cells

Abstract: CAL may downregulate pDCs by inhibiting TLR9-MyD88 signalling.

Cited by 7 publications

References 9 publications

Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2

Regulation of innate immune responses in macrophages differentiated in the presence of vitamin D and infected with dengue virus 2

The Role of Toll-Like Receptors in Skin Host Defense, Psoriasis, and Atopic Dermatitis

The Cancer Prevention, Anti-Inflammatory and Anti-Oxidation of Bioactive Phytochemicals Targeting the TLR4 Signaling Pathway

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