Lipopolysaccharide directly stimulates Th17 differentiation in vitro modulating phosphorylation of RelB and NF-κB1

Park, Joo-Hung; Jeong, Soyeon; Choi, Andy S.; Kim, Soo-Ji

doi:10.1016/j.imlet.2015.03.003

Cited by 55 publications

(38 citation statements)

References 63 publications

(96 reference statements)

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“…Tolerogenic DCs, which can result in T‐cell unresponsiveness, express lower levels of MHC‐II and co‐stimulatory molecules than normal DCs . Our results showed that 1,25(OH) 2 D 3 down‐regulated the expression of MHC‐II, CD86 and CD83 on DCs, and the expression of these surface molecules on VD 3 ‐DCs was still lower than DCs after stimulation with lipopolysaccharide, which is a pro‐inflammatory mediator . These results indicate that VD 3 ‐DCs are a type of steady tolerogenic DC.…”

Section: Discussionmentioning

confidence: 58%

1,25‐dihydroxyvitamin D₃‐induced dendritic cells suppress experimental autoimmune encephalomyelitis by increasing proportions of the regulatory lymphocytes and reducing T helper type 1 and type 17 cells

Xie

Chen

et al. 2017

Immunology

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Dendritic cells (DCs), a bridge for innate and adaptive immune responses, play a key role in the development of multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE), an animal model for MS. Administration of tolerogenic DCs has been used as an immunotherapy in autoimmune diseases. Deficiency of vitamin D is an environmental risk factor of MS. In this study, we induced tolerogenic DCs by 1,25-dihydroxyvitamin D and transferred the tolerogenic DCs (VD -DCs) into EAE mice by adoptive transfer. We found that VD -DCs inhibited the infiltrations of T helper type 1 (Th1) and Th17 cells into spinal cord and increased the proportions of regulatory T cells (CD4 CD25 Foxp3 ), CD4 IL-10 T cells and regulatory B cells (CD19 CD5 CD1d ) in peripheral immune organs, which resulted in attenuated EAE. However, the proportions of T helper type 1 (Th1) and Th17 cells in spleen and lymph nodes and the levels of pro-inflammatory cytokines and IgG in serum also increased after transfer of VD -DCs. We conclude that transfer of VD -DCs suppressed EAE by increasing proportions of regulatory T cells, CD4 IL-10 T cells and regulatory B cells in spleen and reducing infiltration of Th1 and Th17 cells into spinal cord, which suggests a possible immunotherapy method using VD -DCs in MS.

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Section: Discussionmentioning

confidence: 58%

1,25‐dihydroxyvitamin D₃‐induced dendritic cells suppress experimental autoimmune encephalomyelitis by increasing proportions of the regulatory lymphocytes and reducing T helper type 1 and type 17 cells

Xie

Chen

et al. 2017

Immunology

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“…Therefore, we asked whether our 5-d TLR2 tolerance protocol induces crosstolerance to signaling through other TLR molecules. A number of TLRs, including TLR9, TLR7, and TLR4, have been suggested to be important in the pathogenesis of EAE (6,8,(23)(24)(25). Because there has been much evidence that TLR2 and TLR4 usually cross-tolerize each other (22,26), but less documentation that TLR2 can crosstolerize TLR7 and TLR9, we specifically asked whether our TLR2 tolerance induction protocol cross-tolerizes mice to TLR7 and TLR9.…”

Section: Induction Of Tlr2 Tolerance Cross-tolerizes To the Other Tlrmentioning

confidence: 99%

TLR Tolerance as a Treatment for Central Nervous System Autoimmunity

Anstadt

Fujiwara

Wasko

et al. 2016

The Journal of Immunology

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The role of TLR signaling in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE) is unclear. This role is especially controversial in models of adoptive transfer EAE in which no adjuvant and no TLR ligands are administered. We recently reported that a microbiome-derived TLR2 ligand, Lipid 654 (L654), is present in healthy human serum but significantly decreased in the serum of MS patients. This suggested that microbiome products that gain access to the systemic circulation, rather than being proinflammatory, may normally play an immune-regulatory role by maintaining a state of relative TLR tolerance. Therefore, a loss of microbiome-mediated TLR tolerance, as suggested by lower serum levels of L654, may play a role in the pathogenesis of MS. As proof of concept we asked whether administering low-level TLR2 ligands in adoptive transfer EAE induces TLR2 tolerance and attenuates disease. We administered low-level Pam2CSK4 or L654 to mice receiving encephalitogenic cells and in doing so induced both TLR2 tolerance and attenuation of EAE. Disease attenuation was accompanied in the CNS by a decrease in macrophage activation, a decrease in a specific proinflammatory macrophage population, and a decrease in Th17 cells. In addition, disease attenuation was associated with an increase in splenic type 1 regulatory T cells. Kinetic tolerance induction studies revealed a critical period for TLR2 involvement in adoptive transfer EAE. Overall, these results suggest that inducing TLR tolerance may offer a new approach to treating CNS autoimmune diseases such as MS.

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“…They are defined by expression of cell surface markers CD105, CD73, and CD90, lack of expression of hematopoietic markers CD45, CD34, CD11b, CD19, and human leukocyte antigen (HLA)-DR, and their capacity to differentiate in vitro along osteogenic, adipogenic, and chondrogenic pathways [3, 4]. While they are being investigated for regenerative potential, their range of immunomodulatory activities has led to increased focus on this function [5–7]. …”

Section: Introductionmentioning

confidence: 99%

In vitro cytokine licensing induces persistent permissive chromatin at the Indoleamine 2,3-dioxygenase promoter

et al. 2016

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Background Mesenchymal stromal cells (MSCs) are being investigated as therapies for inflammatory diseases due to their immunosuppressive capacity. IFN-γ treatment primes MSC immunosuppression partially through induction of Indoleamine 2,3-dioxygenase (IDO1), which depletes tryptophan necessary to support proliferation of activated T-cells. We investigated the role of histone modifications in the timing and maintenance of induced IDO1 expression in MSCs under clinical manufacturing conditions, such as cryopreservation. Methods We used chromatin immunoprecipitation and quantitative polymerase chain reaction (PCR) to assay levels of transcriptionally permissive acetylated H3K9 and repressive trimethylated H3K9 histone modifications surrounding the transcriptional start site for IDO1, and reverse transcriptase PCR and immunoblotting to detect mRNA and protein. Results MSCs derived from three donors approached maximum IDO1 mRNA levels following 24 hours of in vitro cytokine treatment. Induction of IDO1 expression correlated with increased acetylation of H3K9 concomitant with reduction of trimethylated H3K9 modifications at the promoter. Examination of two additional donors confirmed this result. While induced IDO1 levels declined within two days after cytokine removal and freeze thawing, the activated chromatin state was maintained. Upon re-exposure to cytokines, previously primed MSCs accumulated near-maximum IDO1 mRNA levels within four to eight hours. Discussion Our data indicate that in vitro priming of MSCs causes chromatin remodeling at the IDO1 promoter, that this alteration is maintained during processing commonly used to prepare MSCs for clinical use, and that once primed, MSCs are poised for IDO1 expression even in the absence of cytokines.

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Lipopolysaccharide directly stimulates Th17 differentiation in vitro modulating phosphorylation of RelB and NF-κB1

Cited by 55 publications

References 63 publications

1,25‐dihydroxyvitamin D₃‐induced dendritic cells suppress experimental autoimmune encephalomyelitis by increasing proportions of the regulatory lymphocytes and reducing T helper type 1 and type 17 cells

1,25‐dihydroxyvitamin D₃‐induced dendritic cells suppress experimental autoimmune encephalomyelitis by increasing proportions of the regulatory lymphocytes and reducing T helper type 1 and type 17 cells

TLR Tolerance as a Treatment for Central Nervous System Autoimmunity

In vitro cytokine licensing induces persistent permissive chromatin at the Indoleamine 2,3-dioxygenase promoter

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Lipopolysaccharide directly stimulates Th17 differentiation in vitro modulating phosphorylation of RelB and NF-κB1

Cited by 55 publications

References 63 publications

1,25‐dihydroxyvitamin D3‐induced dendritic cells suppress experimental autoimmune encephalomyelitis by increasing proportions of the regulatory lymphocytes and reducing T helper type 1 and type 17 cells

1,25‐dihydroxyvitamin D3‐induced dendritic cells suppress experimental autoimmune encephalomyelitis by increasing proportions of the regulatory lymphocytes and reducing T helper type 1 and type 17 cells

TLR Tolerance as a Treatment for Central Nervous System Autoimmunity

In vitro cytokine licensing induces persistent permissive chromatin at the Indoleamine 2,3-dioxygenase promoter

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1,25‐dihydroxyvitamin D₃‐induced dendritic cells suppress experimental autoimmune encephalomyelitis by increasing proportions of the regulatory lymphocytes and reducing T helper type 1 and type 17 cells

1,25‐dihydroxyvitamin D₃‐induced dendritic cells suppress experimental autoimmune encephalomyelitis by increasing proportions of the regulatory lymphocytes and reducing T helper type 1 and type 17 cells