A sestrin-dependent Erk-Jnk-p38 MAPK activation complex inhibits immunity during aging

Nature Immunology

Volumn 18, Issue 3, 2017, Pages 354-363

  Lanna, Alessio ^a,b   Gomes, Daniel C O ^a,c   Muller Durovic, Bojana ^a   McDonnell, Thomas ^a   Escors, David ^a,d   Gilroy, Derek W ^a   Lee, Jun Hee ^e   Karin, Michael ^f   Akbar, Arne N ^a  

^a UNIVERSITY COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

^c FEDERAL UNIVERSITY OF ESPÍRITO SANTO   (Brazil)

^d Atención Primaria Y Promoción de La Salud   (Spain)

^e UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

^f UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CD27 ANTIGEN; CD28 ANTIGEN; INFLUENZA VACCINE; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE P38; PROTEIN; SESTRIN; STRESS ACTIVATED PROTEIN KINASE; UNCLASSIFIED DRUG; HEAT SHOCK PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE KINASE 4; SESN1 PROTEIN, HUMAN; SMALL INTERFERING RNA;

ADULT; AGED; ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CD4+ T LYMPHOCYTE; CELL AGING; CELL STRESS; CONTROLLED STUDY; CYTOKINE PRODUCTION; EMBRYO; ENZYME ACTIVATION; ENZYME INHIBITION; FEMALE; HUMAN; HUMAN CELL; INFLUENZA VACCINATION; LYMPHOCYTE PROLIFERATION; MALE; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; SEASONAL INFLUENZA; SENESCENCE; T LYMPHOCYTE; TREATMENT RESPONSE; AGING; ANIMAL; CELL CULTURE; GENETICS; IMMUNITY; IMMUNOLOGY; IMMUNOSENESCENCE; METABOLISM; MIDDLE AGED; PHYSIOLOGY; SIGNAL TRANSDUCTION; VERY ELDERLY; YOUNG ADULT;

ADULT; AGED; AGED, 80 AND OVER; AGING; ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; CELLS, CULTURED; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; FEMALE; HEAT-SHOCK PROTEINS; HUMANS; IMMUNITY; IMMUNOSENESCENCE; MALE; MAP KINASE KINASE 4; MICE; MIDDLE AGED; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION; YOUNG ADULT;

EID: 85010910513     PISSN: 15292908     EISSN: 15292916     Source Type: Journal    
DOI: 10.1038/ni.3665     Document Type: Article

References (39)

1. Montecino-Rodriguez, E., Berent-Maoz, B. & Dorshkind, K. Causes, consequences, and reversal of immune system aging. J. Clin. Invest. 123, 958-965 (2013).
2. Dorshkind, K., Montecino-Rodriguez, E. & Signer, R. A. J. The ageing immune system: is it ever too old to become young again Nat. Rev. Immunol. 9, 57-62 (2009).
3. Lutz, W., Sanderson, W. & Scherbov, S. The coming acceleration of global population ageing. Nature 451, 716-719 (2008).
4. Di Mitri, D. et al. Reversible senescence in human CD4+CD45RA+CD27 memory T cells. J. Immunol. 187, 2093-2100 (2011).
5. Lanna, A., Henson, S. M., Escors, D. & Akbar, A. N. The kinase p38 activated by the metabolic regulator AMPK and scaffold TAB1 drives the senescence of human T cells. Nat. Immunol. 15, 965-972 (2014).
6. Henson, S. M. et al. p38 signaling inhibits mTORC1-independent autophagy in senescent human CD8+ T cells. J. Clin. Invest. 124, 4004-4016 (2014).
7. Li, G. et al. Decline in miR-181a expression with age impairs T cell receptor sensitivity by increasing DUSP6 activity. Nat. Med. 18, 1518-1524 (2012).
8. Müller-Durovic, B. et al. Killer cell lectin-like receptor G1 inhibits NK cell function through activation of adenosine 5-monophosphate-activated protein kinase. J. Immunol. 197, 2891-2899 (2016).
9. Akbar, A. N., Henson, S. M. & Lanna, A. Senescence of T lymphocytes: implications for enhancing human immunity. Trends Immunol. 37, 866-876 (2016).
10. Weng, N.-P., Akbar, A. N. & Goronzy, J. CD28 T cells: their role in the age-associated decline of immune function. Trends Immunol. 30, 306-312 (2009).
11. Chang, L. & Karin, M. Mammalian MAP kinase signalling cascades. Nature 410, 37-40 (2001).
12. Johnson, G. L. & Lapadat, R. Mitogen-activated protein kinase pathways mediated by ERK, Jnk, and p38 protein kinases. Science 298, 1911-1912 (2002).
13. Liu, Y., Shepherd, E. G. & Nelin, L. D. MAPK phosphatases-regulating the immune response. Nat. Rev. Immunol. 7, 202-212 (2007).
14. Chen, R. E. & Thorner, J. Function and regulation in MAPK signaling pathways: lessons learned from the yeast Saccharomyces cerevisiae. Biochim. Biophys. Acta 1773, 1311-1340 (2007).
15. Budanov, A. V. et al. Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability. Oncogene 21, 6017-6031 (2002).
16. Peeters, H. et al. PA26 is a candidate gene for heterotaxia in humans: identification of a novel PA26-related gene family in human and mouse. Hum. Genet. 112, 573-580 (2003).
17. Velasco-Miguel, S. et al. PA26, a novel target of the p53 tumor suppressor and member of the GADD family of DNA damage and growth arrest inducible genes. Oncogene 18, 127-137 (1999).
18. Budanov, A. V. & Karin, M. p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. Cell 134, 451-460 (2008).
19. Hardie, D. G., Ross, F. A. & Hawley, S. A. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat. Rev. Mol. Cell Biol. 13, 251-262 (2012).
20. Lee, J. H. et al. Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies. Science 327, 1223-1228 (2010).
21. Lee, J. H. et al. Maintenance of metabolic homeostasis by Sestrin2 and Sestrin3. Cell Metab. 16, 311-321 (2012).
22. Lee, J. H., Budanov, A. V. & Karin, M. Sestrins orchestrate cellular metabolism to attenuate aging. Cell Metab. 18, 792-801 (2013).
23. Parmigiani, A. et al. Sestrins inhibit mTORC1 kinase activation through the GATOR complex. Cell Rep. 9, 1281-1291 (2014).
24. Peng, M., Yin, N. & Li, M. O. Sestrins function as guanine nucleotide dissociation inhibitors for Rag GTPases to control mTORC1 signaling. Cell 159, 122-133 (2014).
25. Chantranupong, L. et al. The sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1. Cell Rep. 9, 1-8 (2014).
26. Yang, Y.-L. et al. SESN-1 is a positive regulator of lifespan in Caenorhabditis elegans. Exp. Gerontol. 48, 371-379 (2013).
27. Chen, C. C. et al. FoxOs inhibit mTORC1 and activate Akt by inducing the expression of Sestrin3 and Rictor. Dev. Cell 18, 592-604 (2010).
28. Hay, N. p53 strikes mTORC1 by employing sestrins. Cell Metab. 8, 184-185 (2008).
29. Göransson, O. et al. Mechanism of action of A-769662, a valuable tool for activation of AMP-activated protein kinase. J. Biol. Chem. 282, 32549-32560 (2007).
30. Lanna, A. et al. IFN- inhibits telomerase in human CD8+ T cells by both hTERT downregulation and induction of p38 MAPK signaling. J. Immunol. 191, 3744-3752 (2013).
31. Oxman, M. N. et al. A vaccine to prevent herpes zoster and postherpetic neuralgia in older adults. N. Engl. J. Med. 352, 2271-2284 (2005).
32. Levin, M. J. Immune senescence and vaccines to prevent herpes zoster in older persons. Curr. Opin. Immunol. 24, 494-500 (2012).
33. Oh, J. Z. et al. TLR5-mediated sensing of gut microbiota is necessary for antibody responses to seasonal influenza vaccination. Immunity 41, 478-492 (2014).
34. Johnson, S. C., Rabinovitch, P. S. & Kaeberlein, M. mTOR is a key modulator of ageing and age-related disease. Nature 493, 338-345 (2013).
35. Round, J. L. et al. Scaffold protein Dlgh1 coordinates alternative p38 kinase activation, directing T cell receptor signals toward NFAT but not NF-kappaB transcription factors. Nat. Immunol. 8, 154-161 (2007).
36. Ashwell, J. D. The many paths to p38 mitogen-activated protein kinase activation in the immune system. Nat. Rev. Immunol. 6, 532-540 (2006).
37. Akbar, A. N. & Henson, S. M. Are senescence and exhaustion intertwined or unrelated processes that compromise immunity Nat. Rev. Immunol. 11, 289-295 (2011).
38. Escors, D. et al. Targeting dendritic cell signaling to regulate the response to immunization. Blood 111, 3050-3061 (2008).
39. Plunkett, F. J. et al. The loss of telomerase activity in highly differentiated CD8+CD28CD27 T cells is associated with decreased Akt (Ser473) phosphorylation. J. Immunol. 178, 7710-7719 (2007).