IL-6 Produced by Type I IFN DC Controls IFN-γ Production by Regulating the Suppressive Effect of CD4+ CD25+ Regulatory T Cells

2005 ◽  
Vol 66 (5) ◽  
pp. 460-468 ◽  
Author(s):  
Olivier Detournay ◽  
Naima Mazouz ◽  
Michel Goldman ◽  
Michel Toungouz
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Suppressive Effect ◽  
Type I ◽  
Type I Ifn ◽  
Ifn Γ

IL-6 Produced by Type I IFN DC Controls IFN-γ Production during the MLR by Blocking the Suppressive Effect of Regulatory T Cells.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3797-3797
Author(s):  
Olivier Detournay ◽  
Naima Mazouz ◽  
Michel Goldman ◽  
Michel Toungouz
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Mrna Level ◽  
Suppressive Effect ◽  
Poly I:C ◽  
Type I ◽  
Type I Ifn ◽  
Effector Cells ◽  
Gm Csf ◽  
Ifn Γ

Abstract The dendritic cell family is composed of different subsets able to differentially govern the immune response. Their potent antigen presenting properties make them an attractive candidate for immunization against pathogens or cancer. In that setting, the recently characterized type I IFN DCs present interesting features including a higher expression of molecules involved in antigen presentation and the ability to trigger both the cellular and humoral arms of the immune responses. In view of the pivotal role of regulatory T cells in limiting the effectiveness of effector cells, we analyzed the interactions between these cells and type I IFN DC. DC generated from monocytes in the presence of IFN-β and IL-3 (DCI3) were activated by the maturation agent poly I:C and compared with the classical myeloid DC generated in the presence of GM-CSF and IL-4 (DCG4). Despite the release of lower amounts of IL-12 after maturation, DCI3 were able to induce a higher IFN-γ production by T lymphocytes during the MLR. Analysis at the mRNA level disclosed that DCI3 over transcribed the IL-6 gene leading to the release of high amounts of the protein both after the maturation process and during the MLR itself. Neutralization of IL-6 revealed that this cytokine specifically contributed to the IFN-γ release induced by DCI3. Finally, depletion of CD25+ T cells prior to the MLR identified these cells as a target for IL-6. We conclude from these results that DCI3 are endowed with the unique property of blocking the suppressive effect of regulatory T cells through high IL-6 production during the MLR. This novel mechanism of T cell control is relevant for the use of this DC type in vaccination strategies.

scholarly journals Type I IFN gene delivery suppresses regulatory T cells within tumors

2014 ◽  
Vol 21 (12) ◽  
pp. 532-541 ◽  
Author(s):  
H Hashimoto ◽  
R Ueda ◽  
K Narumi ◽  
Y Heike ◽  
T Yoshida ◽  
...  
Keyword(s):  
T Cells ◽  
Gene Delivery ◽  
Regulatory T Cells ◽  
Type I ◽  
Type I Ifn

scholarly journals MiR-146a regulates regulatory T cells to suppress heart transplant rejection in mice

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jian Lu ◽  
Weiwei Wang ◽  
Peiyuan Li ◽  
Xiaodong Wang ◽  
Chao Gao ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Heart Transplant ◽  
Transplant Rejection ◽  
Mouse Heart ◽  
Allograft Survival ◽  
Treg Function ◽  
Ifn Γ ◽  
Heart Transplant Rejection

AbstractRegulatory T cells (Tregs), which characteristically express forkhead box protein 3 (Foxp3), are essential for the induction of immune tolerance. Here, we investigated microRNA-146a (miR-146a), a miRNA that is widely expressed in Tregs and closely related to their homeostasis and function, with the aim of enhancing the function of Tregs by regulating miR-146a and then suppressing transplant rejection. The effect of the absence of miR-146a on Treg function in the presence or absence of rapamycin was detected in both a mouse heart transplantation model and cell co-cultures in vitro. The absence of miR-146a exerted a mild tissue-protective effect by transiently prolonging allograft survival and reducing the infiltration of CD4+ and CD8+ T cells into the allografts. Meanwhile, the absence of miR-146a increased Treg expansion but impaired the ability of Tregs to restrict T helper cell type 1 (Th1) responses. A miR-146a deficiency combined with interferon (IFN)-γ blockade repaired the impaired Treg function, further prolonged allograft survival, and alleviated rejection. Importantly, miR-146a regulated Tregs mainly through the IFN-γ/signal transducer and activator of transcription (STAT) 1 pathway, which is implicated in Treg function to inhibit Th1 responses. Our data suggest miR-146a controls a specific aspect of Treg function, and modulation of miR-146a may enhance Treg efficacy in alleviating heart transplant rejection in mice.

scholarly journals Type I interferons affect the metabolic fitness of CD8+ T cells from patients with systemic lupus erythematosus

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Norzawani Buang ◽  
Lunnathaya Tapeng ◽  
Victor Gray ◽  
Alessandro Sardini ◽  
Chad Whilding ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
T Cells ◽  
Cell Death ◽  
T Cell ◽  
Lupus Erythematosus ◽  
Type I Interferons ◽  
Type I ◽  
Type I Ifn ◽  
Systemic Lupus ◽  
Mitochondrial Abnormalities

AbstractThe majority of patients with systemic lupus erythematosus (SLE) have high expression of type I IFN-stimulated genes. Mitochondrial abnormalities have also been reported, but the contribution of type I IFN exposure to these changes is unknown. Here, we show downregulation of mitochondria-derived genes and mitochondria-associated metabolic pathways in IFN-High patients from transcriptomic analysis of CD4+ and CD8+ T cells. CD8+ T cells from these patients have enlarged mitochondria and lower spare respiratory capacity associated with increased cell death upon rechallenge with TCR stimulation. These mitochondrial abnormalities can be phenocopied by exposing CD8+ T cells from healthy volunteers to type I IFN and TCR stimulation. Mechanistically these ‘SLE-like’ conditions increase CD8+ T cell NAD+ consumption resulting in impaired mitochondrial respiration and reduced cell viability, both of which can be rectified by NAD+ supplementation. Our data suggest that type I IFN exposure contributes to SLE pathogenesis by promoting CD8+ T cell death via metabolic rewiring.

scholarly journals Defective Suppressor Function of Human CD4+ CD25+ Regulatory T Cells in Autoimmune Polyglandular Syndrome Type II

2004 ◽  
Vol 199 (9) ◽  
pp. 1285-1291 ◽  
Author(s):  
Martin A. Kriegel ◽  
Tobias Lohmann ◽  
Christoph Gabler ◽  
Norbert Blank ◽  
Joachim R. Kalden ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Autoimmune Diseases ◽  
Type I ◽  
Type Ii ◽  
Central Tolerance ◽  
Autoimmune Polyglandular Syndrome ◽  
Healthy Donors ◽  
Organ Specific ◽  
Autoimmune Polyglandular Syndrome Type

In autoimmune polyglandular syndromes (APS), several organ-specific autoimmune diseases are clustered. Although APS type I is caused by loss of central tolerance, the etiology of APS type II (APS-II) is currently unknown. However, in several murine models, depletion of CD4+ CD25+ regulatory T cells (Tregs) causes a syndrome resembling human APS-II with multiple endocrinopathies. Therefore, we hypothesized that loss of active suppression in the periphery could be a hallmark of this syndrome. Tregs from peripheral blood of APS-II, control patients with single autoimmune endocrinopathies, and normal healthy donors showed no differences in quantity (except for patients with isolated autoimmune diseases), in functionally important surface markers, or in apoptosis induced by growth factor withdrawal. Strikingly, APS-II Tregs were defective in their suppressive capacity. The defect was persistent and not due to responder cell resistance. These data provide novel insights into the pathogenesis of APS-II and possibly human autoimmunity in general.

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