A novel mechanism for ERK‐dependent regulation of<i>IL4</i>transcription during human Th2‐cell differentiation

Tripathi, Parul; Sahoo, N. C.; Ullah, Ubaid; Kallionpää, Henna; Suneja, Amita; Lahesmaa, Riitta; Rao, Kanury V. S.

doi:10.1038/icb.2011.87

Cited by 36 publications

(31 citation statements)

References 44 publications

(76 reference statements)

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“…These findings are in accordance with the important role of the ERK pathway in T-cell activation (Kortum et al, 2013). On the other hand, despite the critical role of ERK1/2 in Th1 differentiation (Jorritsma et al, 2003;Yamane et al, 2005;Saraiva et al, 2009;Chang et al, 2012;Tripathi et al, 2012), D5R deficiency had no impact on Th1 differentiation (Fig. 4B).…”

Section: Discussionsupporting

confidence: 91%

“…4 and 5). Furthermore, experiments knocking down ERK1/2 with siRNA have demonstrated that Th2 differentiation is impaired and Th1 differentiation is favoured when ERK1/2-mediated signalling is decreased in naive CD4 + T-cells (Tripathi et al, 2012). However, in contrast with our results a marked and sustained ERK1/2 phosphorylation has been associated with differentiation of CD4 + T-cells toward Th1, whereas weak and transient activation of these kinases has been related to Th2 polarization (Jorritsma et al, 2003;Yamane et al, 2005;Saraiva et al, 2009).…”

Section: Discussioncontrasting

confidence: 63%

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Dopamine receptors D3 and D5 regulate CD4+T-cell activation and differentiation by modulating ERK activation and cAMP production

Franz

Contreras

González

et al. 2015

Journal of Neuroimmunology

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Section: Discussionsupporting

confidence: 91%

Section: Discussioncontrasting

confidence: 63%

Dopamine receptors D3 and D5 regulate CD4+T-cell activation and differentiation by modulating ERK activation and cAMP production

Franz

Contreras

González

et al. 2015

Journal of Neuroimmunology

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“…Thus possible mechanisms by which the c-FLIP proteins might alter the gene expression of differentiating Th cells could be the ERK pathway and NF-κB pathway [59]–[61]. Other signaling pathways including p38 MAPK and AP-1 transcription factors have also been linked to c-FLIP activity and expression [31], [62], [63].…”

Section: Discussionmentioning

confidence: 99%

The Regulation and Role of c-FLIP in Human Th Cell Differentiation

et al. 2014

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The early differentiation of T helper (Th) cells is a tightly controlled and finely balanced process, which involves several factors including cytokines, transcription factors and co-stimulatory molecules. Recent studies have shown that in addition to the regulation of apoptosis, caspase activity is also needed for Th cell proliferation and activation and it might play a role in Th cell differentiation. The isoforms of the cellular FLICE inhibitory protein (c-FLIP) are regulators of CASPASE-8 activity and the short isoform, c-FLIPS, has been shown to be up-regulated by IL-4, the Th2 driving cytokine. In this work, we have studied the expression and functional role of three c-FLIP isoforms during the early Th cell differentiation. Only two of the isoforms, c-FLIPS and c-FLIPL, were detected at the protein level although c-FLIPR was expressed at the mRNA level. The knockdown of c-FLIPL led to enhanced Th1 differentiation and elevated IL-4 production by Th2 cells, whereas the knockdown of c-FLIPS diminished GATA3 expression and IL-4 production by Th2 cells. In summary, our results provide new insight into the role of c-FLIP proteins in the early differentiation of human Th cells.

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“…Recent studies have shown that activation of the ERK1/2 signaling pathway can promote the activation and proliferation of T lymphocytes, and inhibit their apoptosis. ERK participates in the transcriptional regulation of IL-4, which is also indispensable for human Th2-cell differentiation [31] . Blockade of ERK activation inhibited Th17-cell development, and interfering with the ERK pathway could present a therapeutic treatment for inflammatory bowel diseases and other Th17-related autoimmune diseases [32] .…”

Section: Discussionmentioning

confidence: 99%

Leptin Is Oversecreted by Respiratory Syncytial Virus-Infected Bronchial Epithelial Cells and Regulates Th2 and Th17 Cell Differentiation

Qin¹,

Bajinka²,

Xiao-ai³

et al. 2015

Int Arch Allergy Immunol

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Background: Infection of human bronchial epithelial cells (hBECs) with respiratory syncytial virus (RSV) has been shown to induce a Th lymphocyte subset drift, e.g. enhanced differentiation of Th2 and Th17 subsets, which is a classic characteristic of asthma. However, the molecules responsible for the drift in Th subsets remain unknown. This study aims to determine the expression of leptin in RSV-infected hBECs, and its role in Th2 and Th17 cell differentiation and extracellular regulated kinase (ERK) 1/2 phosphorylation. Methods: Cultured hBECs were infected with RSV. mRNA expression of the LEP gene in cells was measured by real-time PCR while LEP protein secretion in culture medium was measured by ELISA. Th differentiation was investigated in cultured human peripheral blood mononuclear cells following stimulation with recombinant human leptin. Th2 and Th17 subsets were examined by flow cytometry. Phosphorylation of the ERK1/2 protein in lymphocytes was detected by Western blot and immunofluorescence. Results: LEP mRNA expression was significantly upregulated in RSV-infected hBECs while the leptin protein level in the supernatants of RSV-infected hBECs was significantly increased. Stimulation of lymphocytes with leptin increased the differentiation of the Th17 subset and ERK1/2 phosphorylation, but suppressed Th2 subset differentiation. Conclusion: Leptin was oversecreted by RSV-infected hBECs, which promoted Th17 subset differentiation but suppressed Th2 subset differentiation possibly via regulating ERK1/2 phosphorylation.

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A novel mechanism for ERK‐dependent regulation ofIL4transcription during human Th2‐cell differentiation

Cited by 36 publications

References 44 publications

Dopamine receptors D3 and D5 regulate CD4+T-cell activation and differentiation by modulating ERK activation and cAMP production

Dopamine receptors D3 and D5 regulate CD4+T-cell activation and differentiation by modulating ERK activation and cAMP production

The Regulation and Role of c-FLIP in Human Th Cell Differentiation

Leptin Is Oversecreted by Respiratory Syncytial Virus-Infected Bronchial Epithelial Cells and Regulates Th2 and Th17 Cell Differentiation

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