Interleukin‐7 promotes the survival of human CD4<sup>+</sup> effector/memory T cells by up‐regulating Bcl‐2 proteins and activating the JAK/STAT signalling pathway

Chetoui, Nizar; Boisvert, Marc; Gendron, Steve; Aoudjit, Fawzi

doi:10.1111/j.1365-2567.2009.03244.x

Cited by 109 publications

(102 citation statements)

References 53 publications

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“…A possible explanation for the age-associated proneness to spontaneous apoptosis is the decreases in both IL-7 levels and IL-7 receptor with aging (Kim et al 2006;Kang et al 2004). The IL-7 pathway is necessary for the development and survival of memory T cells by upregulating Bcl-2 pro-survival proteins (Chetoui et al 2010). It would thus be interesting to know whether a training lifestyle can lead to preservation of this pathway, particularly because IL-7 is also secreted by human skeletal muscle cells, and this secretion can be modulated by exercise (Haugen et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Moderate and intense exercise lifestyles attenuate the effects of aging on telomere length and the survival and composition of T cell subpopulations

Silva

Araújo

Fernandes

et al. 2016

AGE

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Studies indicate that exercise might delay human biological aging, but the effects of long-term exercise on T cell function are not well known. We tested the hypothesis that moderate or intense exercise lifestyle may attenuate the effects of aging on the telomere length and the survival and composition of T cell subpopulations. Elderly (65-85 years) with intense training lifestyle (IT, n = 15), moderate training lifestyle (MT, n = 16), and who never trained (NT, n = 15) were studied. Although the three groups presented the ageassociated contraction of the TCD4 + /TCD8 + naïve compartments and expansion of the memory compartments, both training modalities were associated with lower proportion of terminally differentiated (CD45RA + CCR7 neg ) TCD4 + and TCD8 + cells, although among the latter cells, the reduction reached statistical significance only with IT. MT was associated with higher proportion of central memory TCD4 + cells, while IT was associated with higher proportion of effector memory TCD8 + cells. However, both training lifestyles were unable to modify the proportion of senescent (CD28 neg ) TCD8 + cells. Telomeres were longer in T cells in both training groups; with IT, telomere length increased mainly in TCD8 + cells, whereas with MT, a modest increase in telomere length was observed in both TCD8 + and TCD4 + cells. Reduced commitment to apoptosis of resting T cells, as assessed by caspase-3 and Bcl-2 expression, was seen predominantly with IT.

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Section: Discussionmentioning

confidence: 99%

Moderate and intense exercise lifestyles attenuate the effects of aging on telomere length and the survival and composition of T cell subpopulations

Silva

Araújo

Fernandes

et al. 2016

AGE

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“…A more recent report found that IL-7 not only maintained the levels of Mcl-1 but also of Bcl-2 and Bcl-X L , but the analysis there was conducted at 24 h or later of in vitro culture, and therefore secondary effects cannot be judged [25]. Intriguingly, although IL-15 has also been found to stabilise Mcl-1, this effect of IL-15 appears to be conserved between cell types while the effect on Bim is not.…”

Section: Discussionmentioning

confidence: 99%

IL‐15 regulates Bcl‐2 family members Bim and Mcl‐1 through JAK/STAT and PI3K/AKT pathways in T cells

2014

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Maintenance of T cells is determined by their survival capacity, which is regulated by IntroductionDuring maturation and in the mature state, T-cell homeostasis is regulated by two processes: apoptosis and proliferation [1,2]. In resting T cells, apoptosis is largely determined by the Bcl-2 family of proteins, and T-cell survival is regulated by the effect that extrinsic signals have on Bcl-2-family proteins [3]. The main stimuli in the regulation of both proliferation and survival are signals received by common gamma chain cytokines such as IL-7, IL-2 and IL-15, and through the TCR. The main players are similar in the regulation of apoptosis in activated T cells. At the end of the immune response, when the antigen has been cleared, most T cells Correspondence: Dr. Georg Häcker e-mail: georg.haecker@uniklinik-freiburg.de die by apoptosis. Activated T-cell death is probably mostly triggered by the disappearance of cytokines and is also mainly implemented by the Bcl-2 family of proteins, a process also referred to as mitochondrial apoptosis [1,3,4].Of the five established anti-apoptotic Bcl-2 proteins, four have been shown to be involved in the regulation of T-cell survival, namely Bcl-2, Bcl-X L , 5,6]. On the pro-apoptotic side, Bim is the most important trigger of apoptosis [7,8], while weaker activity has also been found for Puma [9,10] and during glucose deprivation for Noxa [11]. These triggers (known as BH3-only proteins) act on Bax and/or Bak, which then implement mitochondrial apoptosis [12].The main players within the apoptotic apparatus are therefore fairly well established. Substantial gaps remain, however, in our understanding how the outside signals are transduced and translated into activation or inhibition of activation of the We previously made the observation that IL-2, IL-7 and IL-15 (all cytokines signalling through the common gamma chain (γ c )), while inhibiting apoptosis in activated T cells, increase rather than decrease the protein levels of pro-apoptotic Bim [16]. In this study, we follow up on that observation and demonstrate that a similar effect is found in resting T cells. During IL-15 stimulation, both phospho-inositol-3-kinase (PI3K) and STAT signalling were necessary for the increase in Bim levels. Bim upregulation was accompanied by increased levels of Bim mRNA. A new STAT5 binding site was identified in the Bim promoter, and binding of STAT5 to this site upon IL-15 stimulation was demonstrated. Mcl-1 was further shown to be upregulated by IL-15, also requiring PI3K and STAT signalling. This suggests that the Bim upregulation is counterbalanced by Mcl-1 and may serve the function of sensitising the cells for quick apoptosis once the survival factor has disappeared. Concurrent CD3 signals also had a varying effect on the induction of Bim or Mcl-1 through γ c -signals, supporting the concept of regulation of Bcl-2 proteins through the concerted action of upstream signal transduction. Results γ c cytokines induce expression of pro-apoptotic Bim while promoting T-cell survivalWe have ...

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“…Therefore, it is reasonable to speculate that the induction of the STAT5 pathway by TSLP and common-g chain family cytokines is related to the corticosteroid resistance in NH cells. In CD4 T lymphocytes, the activation of STAT5 by IL-7 upregulates Bcl-2 and Bcl-xL, protecting the cells from apoptosis 40 . Similarly, TSLP decreased the apoptosis of NH cells with a concomitant induction of Bcl-xL and the induction of Bcl-xL was resistant to corticosteroids.…”

Section: Discussionmentioning

confidence: 99%

Thymic stromal lymphopoietin induces corticosteroid resistance in natural helper cells during airway inflammation

et al. 2013

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Type-2 innate immune responses that occur in airways and are accompanied by goblet-cell hyperplasia and mucus production are largely driven by interleukin-33 (IL-33) and natural helper (NH) cells, a member of group 2 innate lymphoid cells (ILC2s) and the major target of IL-33. Here we report that the corticosteroid resistance observed as a result of airway inflammation triggered by sensitization and exposure to allergen is induced via the IL-33/NHcell axis. Thymic stromal lymphopoietin (TSLP) synthesized during airway inflammation plays a pivotal role in the induction of NH-cell corticosteroid resistance in vitro and in vivo, by controlling phosphorylation of STAT5 and expression of Bcl-xL in NH cells. Blockade of TSLP with a neutralizing antibody or blocking the TSLP/STAT5 signalling pathway with low molecular-weight STAT5 inhibitors such as pimozide restores corticosteroid sensitivity. Thus, the TSLP-STAT5 pathway could be a new therapeutic target in severe, corticosteroid-resistant asthma.

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Interleukin‐7 promotes the survival of human CD4⁺ effector/memory T cells by up‐regulating Bcl‐2 proteins and activating the JAK/STAT signalling pathway

Cited by 109 publications

References 53 publications

Moderate and intense exercise lifestyles attenuate the effects of aging on telomere length and the survival and composition of T cell subpopulations

Moderate and intense exercise lifestyles attenuate the effects of aging on telomere length and the survival and composition of T cell subpopulations

IL‐15 regulates Bcl‐2 family members Bim and Mcl‐1 through JAK/STAT and PI3K/AKT pathways in T cells

Thymic stromal lymphopoietin induces corticosteroid resistance in natural helper cells during airway inflammation

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Interleukin‐7 promotes the survival of human CD4+ effector/memory T cells by up‐regulating Bcl‐2 proteins and activating the JAK/STAT signalling pathway

Cited by 109 publications

References 53 publications

Moderate and intense exercise lifestyles attenuate the effects of aging on telomere length and the survival and composition of T cell subpopulations

Moderate and intense exercise lifestyles attenuate the effects of aging on telomere length and the survival and composition of T cell subpopulations

IL‐15 regulates Bcl‐2 family members Bim and Mcl‐1 through JAK/STAT and PI3K/AKT pathways in T cells

Thymic stromal lymphopoietin induces corticosteroid resistance in natural helper cells during airway inflammation

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Interleukin‐7 promotes the survival of human CD4⁺ effector/memory T cells by up‐regulating Bcl‐2 proteins and activating the JAK/STAT signalling pathway