Revisiting the Concept of Targeting NFAT to Control T Cell Immunity and Autoimmune Diseases

Lee, Jae-Ung; Kim, Li-Kyung; Choi, Je-Min

doi:10.3389/fimmu.2018.02747

Cited by 135 publications

(135 citation statements)

References 207 publications

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“…NFAT family proteins are known to regulate lineage-specific transcription factors during differentiation of T helper 1 (Th1), Th2, Th17, regulatory T (Treg), and follicular helper T cells (Tfh) (Lee, Kim et al, 2018). Interestingly a biphasic role for calcineurin/NFAT signaling during reprogramming has been reported (Khodeer & Era, 2017, Sun et al, 2016.…”

Section: Nfatc2 Is a Critical Target Of Mir-203 Effects During Reprogmentioning

confidence: 99%

miR-203 imposes an intrinsic barrier during cellular reprogramming by targeting NFATC2

Salazar

Martı́nez-Martı́nez

Graña‐Castro

et al. 2020

Preprint

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Cellular reprogramming from somatic to pluripotent cells is the basis for multiple applications aimed to replace damaged tissues in regenerative medicine. However, this process is limited by intrinsic barriers that are induced in response to reprogramming factors. In this manuscript we report that miR-203, a microRNA with multiple functions in differentiation and tumor suppression, acts as an endogenous barrier to reprogramming.Genetic ablation of miR-203 results in enhanced reprogramming whereas its expression prevents the formation of pluripotent cells both in vitro and in vivo. Mechanistically, this effect correlates with the direct repression of NFATC2, a transcription factor involved in the early phases of reprogramming. Inhibition of NFATC2 mimics miR-203 effects whereas NFATC2 overexpression rescues inducible cell pluripotency in miR-203overexpressing cultures. These data suggest that miR-203 repression may favor the efficiency of reprogramming in a variety of cellular models.

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Section: Nfatc2 Is a Critical Target Of Mir-203 Effects During Reprogmentioning

confidence: 99%

miR-203 imposes an intrinsic barrier during cellular reprogramming by targeting NFATC2

Salazar

Martı́nez-Martı́nez

Graña‐Castro

et al. 2020

Preprint

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“…Here, we have assessed NFATc1 isotype (also known as NFAT2), which is predominantly induced post-T-cell activation. NFATc1 isotype is more raised in Th1 and Th2 in comparison to Treg or Th17 subtypes (Lee et al 2018). Previous studies indicate that for successful clearance of C. neoformans infection, a Th1 response is mandatory (Voelz and May 2010).…”

Section: Discussionmentioning

confidence: 99%

T11TS immunotherapy potentiates the repressed calcineurin‐NFAT signalling pathway of T cells in Cryptococcus neoformans infected rats: a cue towards T‐cell activation for antifungal immunity

Faruk

Hazra²,

Mondal³

et al. 2020

J Appl Microbiol

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Aims: To examine the modulation of the interacting partners of the calcineurin (CaN)-NFAT pathway in T cells during Cryptococcus neoformans fungal infection and post-T11TS immunotherapy. Methods and Results: Wistar rats were infected with C. neoformans and followed by immunotherapy with immune-potentiator T11TS. T cells were analysed by flow cytometry, immunoblotting and nuclear translocation study. The signalling proteins LCK, FYN, LAT, PLCc1 and CaN in T cells were regulated by C. neoformans infection resulting in reduced nuclear translocation of NFAT and IL-2 expression. Following T11TS immunotherapy, the expressions of the above-mentioned proteins were boosted and thus resulting in the clearance of C. neoformans from lung and spleen. Conclusions: The precise mechanism of suppression of the T-cell function by C. neoformans is still unknown. Previously, we have shown that T11TS positively regulates the function of T cells to abrogate glioma and other immunosuppressive conditions. T11TS immunotherapy increased the expression of the above signalling partners of the CaN-NFAT pathway in T cells and improved nuclear retention of NFAT. As a result, an increased IL-2 expression leads to activation and proliferation of T cells. Significance and Impact of the Study: Our results demonstrate the role of T11TS in restoring the CaN-NFAT signalling pathway in T cells. It identifies T11TS as an immunotherapeutic agent with potential clinical outcomes to counteract C. neoformans infection.

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“…They are implicated in the development and the function of the immune system, brain, cardiovascular system, skeletal muscles, bones and other organs by regulating the expression of different target genes involved in cytokine production but also in cell proliferation, differentiation and apoptosis. As a consequence, NFAT deregulation is involved in many pathologies including auto-immune diseases, cancer and neurodegenerative diseases (Kipanyula et al, 2016;J.-U. Lee et al, 2018;Müller & Rao, 2010).…”

Section: Introductionmentioning

confidence: 99%

Trim39 regulates neuronal apoptosis by acting as a SUMO-targeted E3 ubiquitin-ligase for the transcription factor NFATc3

Basu-Shrivastava¹,

Mojsa

Mora

et al. 2020

Preprint

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NFATc3 is the predominant member of the NFAT family of transcription factor in neurons, where it plays a pro-apoptotic role. Mechanisms controlling NFAT protein stability are poorly understood. Here we identify Trim39 as an E3 ubiquitin-ligase of NFATc3. Indeed, Trim39 ubiquitinates NFATc3 in vitro and in cells, whereas silencing of endogenous Trim39 decreases NFATc3 ubiquitination. We also show that Trim17 inhibits Trim39-mediated ubiquitination of NFATc3 by reducing both the E3 ubiquitin-ligase activity of Trim39 and the NFATc3/Trim39 interaction. Moreover, mutation of SUMOylation sites in NFATc3 or SUMO-interacting motif in Trim39 reduces the NFATc3/Trim39 interaction and Trim39-induced ubiquitination of NFATc3. As a consequence, silencing of Trim39 increases the protein level and transcriptional activity of NFATc3, resulting in enhanced neuronal apoptosis. Likewise, a SUMOylation-deficient mutant of NFATc3 exhibits increased stability and pro-apoptotic activity. Taken together, these data indicate that Trim39 modulates neuronal apoptosis by acting as a SUMO-targeted E3 ubiquitin-ligase for NFATc3.

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Revisiting the Concept of Targeting NFAT to Control T Cell Immunity and Autoimmune Diseases

Cited by 135 publications

References 207 publications

miR-203 imposes an intrinsic barrier during cellular reprogramming by targeting NFATC2

miR-203 imposes an intrinsic barrier during cellular reprogramming by targeting NFATC2

T11TS immunotherapy potentiates the repressed calcineurin‐NFAT signalling pathway of T cells in Cryptococcus neoformans infected rats: a cue towards T‐cell activation for antifungal immunity

Trim39 regulates neuronal apoptosis by acting as a SUMO-targeted E3 ubiquitin-ligase for the transcription factor NFATc3

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