The chemokine receptor CCR2 maintains plasmacytoid dendritic cell homeostasis

Cédile, Oriane; Jorgensen, Line; Frank, Ida; Włodarczyk, Agnieszka; Owens, Trevor

doi:10.1016/j.imlet.2017.10.012

Cited by 8 publications

(5 citation statements)

References 38 publications

(75 reference statements)

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“…At the same time, the anti-viral ability of natural killer (NK) and B lymphocytes is enhanced, so that pDCs stimulate the innate as well as the acquired immune response, which resembles a bridge between innate immunity and specific immune response (21). It has been observed in vitro that that administration of IFN-α promotes the maturation of pDCs and promotes the production of IL-12, thereby acting on CD40-activated B cells to promote plasma cells and immunoglobulin secretion (22,23). Therefore, pDCs are involved in the activation of T cells, B cells and NK cells.…”

Section: Discussionmentioning

confidence: 99%

Predictive value of plasmacytoid dendritic cells and Toll‑like receptor‑9 regarding the treatment efficacy of interferon‑α in HBeAg‑positive chronic hepatitis B patients

Chen¹,

Yang²,

Tang³

et al. 2019

Exp Ther Med

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Hepatitis B virus (HBV) infection represents a public health threat and a challenge for the medical community. Untimely treatment may lead to liver cirrhosis and even liver cancer. At present, the major treatment for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B patients includes administration of interferon-α (IFN-α), which has anti-viral and immunomodulatory effects. Plasmacytoid dendritic cells (pDCs) and Toll-like receptor-9 (TLR-9) have important roles in anti-viral therapy. However, their predictive value regarding the efficacy of IFN-α treatment of HBeAg-positive chronic hepatitis B (CHB) patients has remained elusive. A total of 178 patients with CHB and HBeAg-positive status, who had not received any previous anti-HBV treatment, were enrolled in the present study. All patients were treated with IFN-α. HBV DNA load, hepatitis B surface antigen and serum alanine aminotransferase were measured prior to and following 48 weeks of treatment. According to HBV levels, the patients were divided into a response group and non-responders group. To determine the amount of pDCs, blood dendritic cell antigen 2 (BDCA-2)- and immunoglobulin-like transcript 7 (ILT7)-expressing cells in liver biopsies were detected using immunohistochemistry. TLR-9 expression in peripheral blood mononuclear cells was determined by reverse transcription-quantitative PCR. There was no significant difference in the proportion of pDCs (BDCA-2; ILT7) and TLR-9 mRNA expression between the response group and the non-responders group prior to IFN-α treatment. After IFN-α treatment, BDCA-2, ILT7 and TLR-9 mRNA expression was obviously increased in the response group compared with that in the non-responders group (P<0.05). Increased expression of BDCA-2, ILT7 and TLR-9 mRNA was negatively correlated with HBV DNA (P<0.05). Increased levels of pDCs and TLR-9 were negatively correlated with HBV DNA, and were thus capable of predicting the IFN-α treatment response in patients with CHB and HBeAg-positive status.

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Section: Discussionmentioning

confidence: 99%

Predictive value of plasmacytoid dendritic cells and Toll‑like receptor‑9 regarding the treatment efficacy of interferon‑α in HBeAg‑positive chronic hepatitis B patients

Chen¹,

Yang²,

Tang³

et al. 2019

Exp Ther Med

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show abstract

“…3a ). Since we and others previously showed that CCL2 overexpression in the thymus leads to increased thymic pDC cellularity and that its receptor CCR2 is involved in thymic SHPS-1 + cDC and pDC homeostasis 19 , 34 , 35 , we hypothesised that LTα could modulate CCL2 expression. Strikingly, Ccl2 expression was substantially higher in both total thymus ( p < 0.05 by a two-tailed Mann–Whitney test) and purified mTECs ( p < 0.05 by a two-tailed Mann-Whitney test) in Ltα −/− mice than in WT mice (Fig.…”

Section: Resultsmentioning

confidence: 97%

Lymphotoxin α fine-tunes T cell clonal deletion by regulating thymic entry of antigen-presenting cells

et al. 2018

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Medullary thymic epithelial cells (mTEC) purge the T cell repertoire of autoreactive thymocytes. Although dendritic cells (DC) reinforce this process by transporting innocuous peripheral self-antigens, the mechanisms that control their thymic entry remain unclear. Here we show that mTEC-CD4+ thymocyte crosstalk regulates the thymus homing of SHPS-1+ conventional DCs (cDC), plasmacytoid DCs (pDC) and macrophages. This homing process is controlled by lymphotoxin α (LTα), which negatively regulates CCL2, CCL8 and CCL12 chemokines in mTECs. Consequently, Ltα-deficient mice have increased expression of these chemokines that correlates with augmented classical NF-κB subunits and increased thymic recruitment of cDCs, pDCs and macrophages. This enhanced migration depends mainly on the chemokine receptor CCR2, and increases thymic clonal deletion. Altogether, this study identifies a fine-tuning mechanism of T cell repertoire selection and paves the way for therapeutic interventions to treat autoimmune disorders.

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“…4 e). Among these genes, we found that 11 genes (VCAM1 [ 58 ], PTPN22 [ 59 ], ICAM1 [ 60 ], IL7R [ 61 ], TNFSF14 [ 62 ], GPR174 [ 63 ], CCR2 [ 64 ], CCR4 [ 65 ], CTLA4 [ 66 ], LYN [ [67] , [68] , [69] ] and RUNX3 [ 70 ]) were essential for dendritic cell development, maturation, activation and other functions. Spearman’s correlation analysis between genes and ESTIMATE analysis also showed that these dendritic cell-associated genes were positive associated with ESTIMATE Score and were negative associated with Tumor Purity ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Cluster 2 (GLS expressed high and GOT2 expressed low) breast cancer showed a higher association with dendritic cells, implying that GLS and GOT2 may also be involved in dendritic cell regulation. Further gene expression correlation analysis found dendritic cell-associated genes (VCAM1 [ 58 ], PTPN22 [ 59 ], ICAM1 [ 60 ], IL7R [ 61 ], TNFSF14 [ 62 ], GPR174 [ 63 ], CCR2 [ 64 ], CCR4 [ 65 ], CTLA4 [ 66 ], LYN [ [67] , [68] , [69] ] and RUNX3 [ 70 ]), suggesting that glutamine metabolism regulated by GLS and GOT2 may play important roles in dendritic cell development maturation, activation and other functions of dendritic cells. The association between the expressions of GLS and GOT2 and dendritic cells may provide a new clue regarding how glutamine metabolism regulates antitumor immunity.…”

Section: Conclusion and Discussionmentioning

confidence: 99%

GLS and GOT2 as prognostic biomarkers associated with dendritic cell and immunotherapy response in breast cancer

Yang,

Cheng,

Xiao

et al. 2024

Heliyon

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The chemokine receptor CCR2 maintains plasmacytoid dendritic cell homeostasis

Cited by 8 publications

References 38 publications

Predictive value of plasmacytoid dendritic cells and Toll‑like receptor‑9 regarding the treatment efficacy of interferon‑α in HBeAg‑positive chronic hepatitis B patients

Predictive value of plasmacytoid dendritic cells and Toll‑like receptor‑9 regarding the treatment efficacy of interferon‑α in HBeAg‑positive chronic hepatitis B patients

Lymphotoxin α fine-tunes T cell clonal deletion by regulating thymic entry of antigen-presenting cells

GLS and GOT2 as prognostic biomarkers associated with dendritic cell and immunotherapy response in breast cancer

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