mTORC1 Promotes T-bet Phosphorylation To Regulate Th1 Differentiation

Chornoguz, Olesya; Hagan, Robert S.; Haile, Azeb; Arwood, Matthew L.; Gamper, Christopher; Banerjee, Arnob; Powell, Jonathan D.

doi:10.4049/jimmunol.1601078

Cited by 38 publications

(35 citation statements)

References 36 publications

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“…64 mTORC1 signaling is essential for T cell development in the thymus, homeostasis in the periphery and differentiation into effector CD4 + Th1, Th2 and Th17 cells, as well as cytotoxic CD8 + T cells. 2,[29][30][31][65][66][67][68][69] By contrast, mTORC2 activity is more selectively required for Th1 and Th2 cell differentiation, 29,30 but also regulates migration of Tfh and Treg cells. 70,71 mTOR signaling plays an additional role in the antagonism of conventional T cell responses, by regulating the activation, lineage stability and suppressive function of Treg cells in vivo.…”

Section: Agc Kinasesmentioning

confidence: 99%

Signaling networks in immunometabolism

Saravia¹,

Raynor²,

Chapman³

et al. 2020

Cell Res

137

136

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Adaptive immunity is essential for pathogen and tumor eradication, but may also trigger uncontrolled or pathological inflammation. T cell receptor, co-stimulatory and cytokine signals coordinately dictate specific signaling networks that trigger the activation and functional programming of T cells. In addition, cellular metabolism promotes T cell responses and is dynamically regulated through the interplay of serine/threonine kinases, immunological cues and nutrient signaling networks. In this review, we summarize the upstream regulators and signaling effectors of key serine/threonine kinase-mediated signaling networks, including PI3K-AGC kinases, mTOR and LKB1-AMPK pathways that regulate metabolism, especially in T cells. We also provide our perspectives about the pending questions and clinical applicability of immunometabolic signaling. Understanding the regulators and effectors of immunometabolic signaling networks may uncover therapeutic targets to modulate metabolic programming and T cell responses in human disease.

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Section: Agc Kinasesmentioning

confidence: 99%

Signaling networks in immunometabolism

Saravia¹,

Raynor²,

Chapman³

et al. 2020

Cell Res

137

136

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“…187 Further analysis of CD4 + T cells lacking RHEB shows impairment of Th1-cell differentiation without a substantial effect on Th2-cell differentiation, associated with reduced STAT4 phosphorylation in response to IL-12 158 or through control of T-bet phosphorylation. 193 Interestingly, complete ablation of mTORC1 activation via RAPTOR deletion also reduces Th2-cell differentiation. 22 The observation that RAPTOR, but not RHEB, deficiency attenuates…”

Section: Expressing T Cells (Called Peripherally Induced Treg [Ptreg]mentioning

confidence: 99%

mTOR signaling at the crossroads of environmental signals and T‐cell fate decisions

Huang

Long

Zhou

et al. 2020

Immunological Reviews

124

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The evolutionarily conserved serine/threonine kinase mTOR (mechanistic target of rapamycin) forms the distinct protein complexes mTORC1 and mTORC2 and integrates signals from the environment to coordinate downstream signaling events and various cellular processes. T cells rely on mTOR activity for their development and to establish their homeostasis and functional fitness. Here, we review recent progress in our understanding of the upstream signaling and downstream targets of mTOR. We also provide an updated overview of the roles of mTOR in T‐cell development, homeostasis, activation, and effector‐cell fate decisions, as well as its important impacts on the suppressive activity of regulatory T cells. Moreover, we summarize the emerging roles of mTOR in T‐cell exhaustion and transdifferentiation. A better understanding of the contribution of mTOR to T‐cell fate decisions will ultimately aid in the therapeutic targeting of mTOR in human disease.

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“…mTOR signaling is also a central regulator of cellular metabolism and T cell responses [ 107 ]. mTORC1 signaling is important for T cell development in the thymus; homeostasis in the periphery; and differentiation into CD4 + Th1, Th2, and Th17 cells, as well as cytotoxic CD8 + T cells [ 110 , 111 , 112 ]. mTORC2 is required for Th1 and Th2 cell differentiation [ 113 ].…”

Section: Role Of Gut Microbiota In Host Energy Metabolism and Immumentioning

confidence: 99%

Involvement of Gut Microbiota, Microbial Metabolites and Interaction with Polyphenol in Host Immunometabolism

Man¹,

Zhou²,

Xia³

et al. 2020

Nutrients

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Immunological and metabolic processes are inextricably linked and important for maintaining tissue and organismal health. Manipulation of cellular metabolism could be beneficial to immunity and prevent metabolic and degenerative diseases including obesity, diabetes, and cancer. Maintenance of a normal metabolism depends on symbiotic consortium of gut microbes. Gut microbiota contributes to certain xenobiotic metabolisms and bioactive metabolites production. Gut microbiota-derived metabolites have been shown to be involved in inflammatory activation of macrophages and contribute to metabolic diseases. Recent studies have focused on how nutrients affect immunometabolism. Polyphenols, the secondary metabolites of plants, are presented in many foods and beverages. Several studies have demonstrated the antioxidant and anti-inflammatory properties of polyphenols. Many clinical trials and epidemiological studies have also shown that long-term consumption of polyphenol-rich diet protects against chronic metabolic diseases. It is known that polyphenols can modulate the composition of core gut microbiota and interact with the immunometabolism. In the present article, we review the mechanisms of gut microbiota and its metabolites on immunometabolism, summarize recent findings on how the interaction between microbiota and polyphenol modulates host immunometabolism, and discuss future research directions.

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mTORC1 Promotes T-bet Phosphorylation To Regulate Th1 Differentiation

Cited by 38 publications

References 36 publications

Signaling networks in immunometabolism

Signaling networks in immunometabolism

mTOR signaling at the crossroads of environmental signals and T‐cell fate decisions

Involvement of Gut Microbiota, Microbial Metabolites and Interaction with Polyphenol in Host Immunometabolism

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