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Ron D., and Walter P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat Rev Mol Cell Biol 8 (2007) 519-529
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(2007)
Nat Rev Mol Cell Biol
, vol.8
, pp. 519-529
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Ron, D.1
Walter, P.2
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43
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50249116184
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The endoplasmic reticulum stress response in immunity and autoimmunity
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Todd D.J., Lee A.H., and Glimcher L.H. The endoplasmic reticulum stress response in immunity and autoimmunity. Nat Rev Immunol 8 (2008) 663-674
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(2008)
Nat Rev Immunol
, vol.8
, pp. 663-674
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Todd, D.J.1
Lee, A.H.2
Glimcher, L.H.3
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44
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19344377474
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GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase
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This paper demonstrates the central role of the GCN2 stress kinase in sensing tryptophane depletion and arresting T cells in response to IDO. GCN2-knockout T cells were not inhibited by IDO-expressing DCs from tumor-draining lymph nodes. IDO induced profound anergy in responding wild-type T cells, but GCN2-knockout cells were refractory to IDO-induced anergy. GCN2 acts as a molecular sensor in T cells, allowing them to detect and respond to conditions created by IDO. Thus GCN2 and its target eIF2-α are key molecules for tolerance establishment and the subversion of the immune system by tumors.
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Munn D.H., Sharma M.D., Baban B., Harding H.P., Zhang Y., Ron D., and Mellor A.L. GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase. Immunity 22 (2005) 633-642. This paper demonstrates the central role of the GCN2 stress kinase in sensing tryptophane depletion and arresting T cells in response to IDO. GCN2-knockout T cells were not inhibited by IDO-expressing DCs from tumor-draining lymph nodes. IDO induced profound anergy in responding wild-type T cells, but GCN2-knockout cells were refractory to IDO-induced anergy. GCN2 acts as a molecular sensor in T cells, allowing them to detect and respond to conditions created by IDO. Thus GCN2 and its target eIF2-α are key molecules for tolerance establishment and the subversion of the immune system by tumors.
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(2005)
Immunity
, vol.22
, pp. 633-642
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Munn, D.H.1
Sharma, M.D.2
Baban, B.3
Harding, H.P.4
Zhang, Y.5
Ron, D.6
Mellor, A.L.7
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45
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34248173331
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Indoleamine 2,3-dioxygenase and tumor-induced tolerance
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Munn D.H., and Mellor A.L. Indoleamine 2,3-dioxygenase and tumor-induced tolerance. J Clin Invest 117 (2007) 1147-1154
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(2007)
J Clin Invest
, vol.117
, pp. 1147-1154
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Munn, D.H.1
Mellor, A.L.2
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46
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34848915783
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Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase
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Sharma M.D., Baban B., Chandler P., Hou D.Y., Singh N., Yagita H., Azuma M., Blazar B.R., Mellor A.L., and Munn D.H. Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase. J Clin Invest 117 (2007) 2570-2582
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(2007)
J Clin Invest
, vol.117
, pp. 2570-2582
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Sharma, M.D.1
Baban, B.2
Chandler, P.3
Hou, D.Y.4
Singh, N.5
Yagita, H.6
Azuma, M.7
Blazar, B.R.8
Mellor, A.L.9
Munn, D.H.10
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47
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33744465772
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Activation of the integrated stress response during T helper cell differentiation
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After priming via signals through the T-cell receptor, naive T helper cells express cytokine mRNA but do not secrete cytokine protein without additional T cell receptor stimulation. This article demonstrates that primed T cells phosphorylate the eukaryotic initiation factor 2-α and accumulate cytoplasmic granules associated with RNA-binding proteins. Restimulation of the cells resulted in rapid eIF2-α dephosphorylation, ribosomal mRNA loading, and cytokine secretion.
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Scheu S., Stetson D.B., Reinhardt R.L., Leber J.H., Mohrs M., and Locksley R.M. Activation of the integrated stress response during T helper cell differentiation. Nat Immunol 7 (2006) 644-651. After priming via signals through the T-cell receptor, naive T helper cells express cytokine mRNA but do not secrete cytokine protein without additional T cell receptor stimulation. This article demonstrates that primed T cells phosphorylate the eukaryotic initiation factor 2-α and accumulate cytoplasmic granules associated with RNA-binding proteins. Restimulation of the cells resulted in rapid eIF2-α dephosphorylation, ribosomal mRNA loading, and cytokine secretion.
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(2006)
Nat Immunol
, vol.7
, pp. 644-651
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Scheu, S.1
Stetson, D.B.2
Reinhardt, R.L.3
Leber, J.H.4
Mohrs, M.5
Locksley, R.M.6
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48
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34250200713
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Acquisition of murine NK cell cytotoxicity requires the translation of a pre-existing pool of granzyme B and perforin mRNAs
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In this article, the role of eIF2-α phosphorylation in the acquisition of cytotoxic activity of mouse NK cells is demonstrated. Although activated murine NK cells can use the granule exocytosis pathway to kill target cells immediately upon recognition, resting murine NK cells are minimally cytotoxic. It is shown that resting murine NK cells are minimally cytotoxic because of a block in perforin and granzyme B mRNA translation that is released by NK cell activation.
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Fehniger T.A., Cai S.F., Cao X., Bredemeyer A.J., Presti R.M., French A.R., and Ley T.J. Acquisition of murine NK cell cytotoxicity requires the translation of a pre-existing pool of granzyme B and perforin mRNAs. Immunity 26 (2007) 798-811. In this article, the role of eIF2-α phosphorylation in the acquisition of cytotoxic activity of mouse NK cells is demonstrated. Although activated murine NK cells can use the granule exocytosis pathway to kill target cells immediately upon recognition, resting murine NK cells are minimally cytotoxic. It is shown that resting murine NK cells are minimally cytotoxic because of a block in perforin and granzyme B mRNA translation that is released by NK cell activation.
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(2007)
Immunity
, vol.26
, pp. 798-811
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Fehniger, T.A.1
Cai, S.F.2
Cao, X.3
Bredemeyer, A.J.4
Presti, R.M.5
French, A.R.6
Ley, T.J.7
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49
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1642617628
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The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4
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Hsu L.C., Park J.M., Zhang K., Luo J.L., Maeda S., Kaufman R.J., Eckmann L., Guiney D.G., and Karin M. The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4. Nature 428 (2004) 341-345
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(2004)
Nature
, vol.428
, pp. 341-345
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Hsu, L.C.1
Park, J.M.2
Zhang, K.3
Luo, J.L.4
Maeda, S.5
Kaufman, R.J.6
Eckmann, L.7
Guiney, D.G.8
Karin, M.9
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50
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47849125676
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MicroRNAs: new regulators of immune cell development and function
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Baltimore D., Boldin M.P., O'Connell R.M., Rao D.S., and Taganov K.D. MicroRNAs: new regulators of immune cell development and function. Nat Immunol 9 (2008) 839-845
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(2008)
Nat Immunol
, vol.9
, pp. 839-845
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Baltimore, D.1
Boldin, M.P.2
O'Connell, R.M.3
Rao, D.S.4
Taganov, K.D.5
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