microRNAs function in CD8+T cell biology

Liang, Yan; Pan, Hai‐Feng; Ye, Dong-Qing

doi:10.1189/jlb.1ru0814-369r

Cited by 40 publications

(38 citation statements)

References 99 publications

(156 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The expression of miR‐155 in T cells is induced upon TCR stimulation and nuclear factor (NF)‐κB signalling. By repressing SHIP1, miR‐155 expression induces effector functions such as IFN‐γ secretion . We showed that miR‐155 expression in G‐CSF‐treated and ‐untreated CD8 + T cells was induced after TCR stimulation, which is consistent with the model proposed by Liang et al .…”

Section: Discussionsupporting

confidence: 89%

“…By repressing SHIP1, miR-155 expression induces effector functions such as IFN-g secretion [14,[41][42][43]. We showed that miR-155 expression in G-CSF-treated and -untreated CD8 1 T cells was induced after TCR stimulation, which is consistent with the model proposed by Liang et al in 2015 [14]. Importantly, the induction of miR-155 expression was lower in G-CSF-treated CD8 1 T cells than in untreated cells.…”

Section: G-csf Affects the Main Elements Of T Cell Activationsupporting

confidence: 90%

See 1 more Smart Citation

Granulocyte colony-stimulating factor impairs CD8+ T cell functionality by interfering with central activation elements

Bunse

Tischer

Lahrberg

et al. 2016

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SummaryBesides mobilizing stem cells into the periphery, granulocyte colonystimulating factor (G-CSF) has been shown to influence various types of innate and adaptive immune cells. For example, it impairs the effector function of cytotoxic T lymphocytes (CTLs). It is assumed that this effect is mediated indirectly by monocytes, regulatory T cells and immunomodulatory cytokines influenced by G-CSF. In this study, isolated G-CSF-treated CD8 1 T cells were stimulated antigen-dependently with peptide-major histocompatibility complex (pMHC)-coupled artificial antigen-presenting cells (aAPCs) or stimulated antigen-independently with anti-CD3/CD28 stimulator beads. By measuring the changes in interferon (IFN)-g and granzyme B expression at the mRNA and protein level, we showed for the first time that G-CSF has a direct effect on CD8 1 CTLs, which was confirmed based on the reduced production of IFN-g and granzyme B by the cytotoxic T cell line TALL-104 after G-CSF treatment. By investigating further elements affected by G-CSF in CTLs from stem cell donors and untreated controls, we found a decreased phosphorylation of extracellular-regulated kinase (ERK)1/2, lymphocytespecific protein tyrosine kinase (Lck) and CD3f after G-CSF treatment. Additionally, miRNA-155 and activation marker expression levels were reduced. In summary, our results show that G-CSF directly influences the effector function of cytotoxic CD8 1 T cells and affects various elements of T cell activation.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: G-csf Affects the Main Elements Of T Cell Activationsupporting

confidence: 90%

Granulocyte colony-stimulating factor impairs CD8+ T cell functionality by interfering with central activation elements

Bunse

Tischer

Lahrberg

et al. 2016

Clinical and Experimental Immunology

View full text Add to dashboard Cite

show abstract

“…Their ubiquity makes them potential targets for treatment. Several miRNAs have been shown to alter the activity of APCs, NK cells, T cell differentiation, and effector capacity in mycobacterial infections [32,33]. In a case-control study that enrolled 1098 individuals, single nucleotide polymorphisms located in predicted miR-146a was a unique gene associated with increased risk of leprosy and modulation of TNF levels [34].…”

Section: Mirnamentioning

confidence: 99%

Leprosy as a model to understand cancer immunosurveillance and T cell anergy

Park

Rendini

Martiniuk³

et al. 2016

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Leprosy is a disease caused by Mycobacterium leprae that presents on a spectrum of both clinical manifestations and T cell response. On one end of this spectrum, tuberculoid leprosy is a well-controlled disease, characterized by a cell-mediated immunity and immunosurveillance. On the opposite end of the spectrum, lepromatous leprosy is characterized by M. leprae proliferation and T cell anergy. Similar to progressive tumor cells, M. leprae escapes immunosurveillance in more severe forms of leprosy. The mechanisms by which M. leprae is able to evade the host immune response involve many, including the alterations of lipid droplets, microRNA, and Schwann cells, and involve the regulation of immune regulators, such as the negative checkpoint regulators CTLA-4, programmed death 1, and V-domain Ig suppressor of T cell activation-important targets in today's cancer immunotherapies. The means by which tumor cells become able to escape immunosurveillance through negative checkpoint regulators are evidenced by the successes of treatments, such as nivolumab and ipilimumab. Many parallels can be drawn between the immune responses seen in leprosy and cancer. Therefore, the understanding of how M. leprae encourages immune escape during proliferative disease states has potential to add to our understanding of cancer immunotherapy.

show abstract

“…On cellular level, 71 of 420 highly characterized miRNAs are differentially expressed upon human T cell activation in vitro[ 8 ]. miRNAs regulate multiple functions in T cells such as TCR signaling, proliferation, differentiation, cytokine secretion and apoptosis[ 9 ] E.g. miR-146a upregulation upon TCR stimulation increases the overall TCR signaling and, thereby, enhances cell activation and cell expansion[ 10 ] miR-155 targets SOCS1, Ship1 and many other mRNAs that participate in type 1 interferon (IFN) signaling and promotes CD8+ T cell proliferation and survival[ 11 , 12 ] miR-17-92 targets the tumor suppressors Pten, ID2, ID3 and the anti-apoptotic bcl-2 and enhances the cell cycle progression of T cells[ 13 ].…”

Section: Introductionmentioning

confidence: 99%

miR-625-3p is upregulated in CD8+ T cells during early immune reconstitution after allogeneic stem cell transplantation

et al. 2017

View full text Add to dashboard Cite

Alloreactive CD8+ T-cells mediate the curative graft-versus-leukaemia effect, the anti-viral immunity and graft-versus-host-disease (GvHD) after allogeneic stem cell transplantation (SCT). Thus, immune reconstitution with CD8+ T-cells is critical for the outcome of patients after allogeneic SCT. Certain miRNAs such as miR-146a or miR-155 play an important role in the regulation of post-transplant immunity in mice. While some miRNAs e.g. miR-423 or miR-155 are regulated in plasma or full blood during acute GvHD also in man, the relevance and expression profile of miRNAs in T-cells after allogeneic SCT is unknown. miR-625-3p has recently been described to be overexpressed in colorectal malignancies where it promotes migration, invasion and apoptosis resistance. Since similar regulative functions in cancer and T-cells have been described for an increasing number of miRNAs, we assumed a role for the cancer-related miR-625-3p also in T-cells. Here, we studied miR-625-3p expression selectively in CD8+ T-cells both in vitro and during immune reconstitution after allogeneic SCT in man. T-cell receptor stimulation lead to miR-625-3p upregulation in human CD8+ T-cells in vitro. Maintenance of elevated miR-625-3p expression levels was dependent on ongoing T-cell proliferation and was abrogated by withdrawal of interleukin 2 or the mTOR inhibitor rapamycin. Finally, miR-625-3p expression was analyzed in human CD8+ T-cells purified from 137 peripheral blood samples longitudinally collected from 74 patients after allogeneic SCT. miR-625-3p expression was upregulated on day 25 and on day 45, i.e. during the early phase of CD8+ T-cell reconstitution after allogeneic SCT and subsequently declined with completion of CD8+ T-cell reconstitution until day 150. In conclusion, this study has shown for the first time that miR-625-3p is regulated in CD8+ T-cells during proliferation in vitro and during early immune reconstitution after allogeneic SCT in vivo. These results warrant further studies to identify the targets and function of miR-625-3p in CD8+ T-cells and to analyze its predictive value for an effective immune reconstitution.

show abstract

microRNAs function in CD8+T cell biology

Abstract: ABSTRACT

Cited by 40 publications

References 99 publications

Granulocyte colony-stimulating factor impairs CD8+ T cell functionality by interfering with central activation elements

Granulocyte colony-stimulating factor impairs CD8+ T cell functionality by interfering with central activation elements

Leprosy as a model to understand cancer immunosurveillance and T cell anergy

miR-625-3p is upregulated in CD8+ T cells during early immune reconstitution after allogeneic stem cell transplantation

Contact Info

Product

Resources

About