LXR-dependent and -independent effects of oxysterols on immunity and tumor growth

European Journal of Immunology

Volumn 44, Issue 7, 2014, Pages 1896-1903

  Traversari, Catia ^a   Sozzani, Silvano ^b,c   Steffensen, Knut R ^d   Russo, Vincenzo ^e  

^a MOLMED S P A   (Italy)

^b UNIVERSITY OF BRESCIA   (Italy)

^c HUMANITAS CLINICAL AND RESEARCH CENTER   (Italy)

^d KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

^e SAN RAFFAELE HOSPITAL   (Italy)

Author keywords

Antitumor immune responses; Liver X receptor(s); Oxysterols

Indexed keywords

ANTITUMOR IMMUNE RESPONSES; LIVER X RECEPTOR(S); OXYSTEROLS;

ANIMALS; CHOLESTEROL; DENDRITIC CELLS; HUMANS; HYDROXYCHOLESTEROLS; IMMUNITY; LYMPHOCYTES; MACROPHAGES; MONOCYTES; NEOPLASMS; ORPHAN NUCLEAR RECEPTORS; RECEPTORS, CCR7; TUMOR MICROENVIRONMENT;

EID: 84904400209     PISSN: 00142980     EISSN: 15214141     Source Type: Journal    
DOI: 10.1002/eji.201344292     Document Type: Review

References (56)

1. Goldstein, J. L., Debose-Boyd, R. A. and Brown, M. S., Protein sensors for membrane sterols. Cell 2006. 124: 35-46.
2. Bjorkhem, I., Do oxysterols control cholesterol homeostasis? J. Clin. Invest. 2002. 110: 725-730.
3. Smith, W. L. and Murphy, R. C., Oxidized lipids formed non-enzymatically by reactive oxygen species. J. Biol. Chem. 2008. 283: 15513-15514.
4. Mast, N., Annalora, A. J., Lodowski, D. T., Palczewski, K., Stout, C. D. and Pikuleva, I. A., Structural basis for three-step sequential catalysis by the cholesterol side chain cleavage enzyme Cyp11a1. J. Biol. Chem. 2011. 286: 5607-5613.
5. Murphy, R. C. and Johnson, K. M., Cholesterol, reactive oxygen species, and the formation of biologically active mediators. J. Biol. Chem. 2008. 283: 15521-15525.
6. Spann, N. J., Garmire, L. X., Mcdonald, J. G., Myers, D. S., Milne, S. B., Shibata, N., Reichart, D. et al., Regulated accumulation of desmosterol integrates macrophage lipid metabolism and inflammatory responses. Cell 2012. 151: 138-152.
7. Peet, D. J., Janowski, B. A. and Mangelsdorf, D. J., The LXRs: a new class of oxysterol receptors. Curr. Opin. Genet. Dev. 1998. 8: 571-575.
8. Yang, X., Lamia, K. A. and Evans, R. M., Nuclear receptors, metabolism, and the circadian clock. Cold Spring Harb. Symp. Quant. Biol. 2007. 72: 387-394.
9. Kalaany, N. Y. and Mangelsdorf, D. J., LXRs and FXR: the yin and yang of cholesterol and fat metabolism. Annu. Rev. Physiol. 2006. 68: 159-191.
10. Villablanca, E. J., Raccosta, L., Zhou, D., Fontana, R., Maggioni, D., Negro, A., Sanvito, F. et al., Tumor-mediated liver X receptor-alpha activation inhibits Cc chemokine receptor-7 expression on dendritic cells and dampens antitumor responses. Nat. Med. 2010. 16: 98-105.
11. Glass, C. K. and Rosenfeld, M. G., The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev. 2000. 14: 121-141.
12. Joseph, S. B., Castrillo, A., Laffitte, B. A., Mangelsdorf, D. J. and Tontonoz, P., Reciprocal regulation of inflammation and lipid metabolism by liver x receptors. Nat. Med. 2003. 9: 213-219.
13. Glass, C. K. and Saijo, K., Nuclear receptor transrepression pathways that regulate inflammation in macrophages and T cells. Nat. Rev. Immunol. 2010. 10: 365-376.
14. Traversari, C. and Russo, V., Control of the immune system by oxysterols and cancer development. Curr. Op Pharmacol. 2012. 12: 729-735.
15. Bensinger, S. J. and Tontonoz, P., Integration of metabolism and inflammation by lipid-activated nuclear receptors. Nature 2008. 454: 470-477.
16. Spann, N. J. and Glass, C. K., Sterols and oxysterols in immune cell function. Nat. Immunol. 2013. 14: 893-900.
17. Joseph, S. B., Bradley, M. N., Castrillo, A., Bruhn, K. W., Mak, P. A., Pei, L., Hogenesch, J. et al., LXR-dependent gene expression is important for macrophage survival and the innate immune response. Cell 2004. 119: 299-309.
18. Valledor, A. F., Hsu, L. C., Ogawa, S., Sawka-Verhelle, D., Karin, M. and Glass, C. K., Activation of liver X receptors and retinoid X receptors prevents bacterial-induced macrophage apoptosis. Proc. Natl. Acad. Sci. USA 2004. 101: 17813-17818.
19. A-Gonzalez, N., Bensinger, S. J., Hong, C., Beceiro, S., Bradley, M. N., Zelcer, N., Deniz, J. et al., Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR. Immunity 2009. 31: 245-258.
20. Roncarolo, M. G., Levings, M. K. and Traversari, C., Differentiation of T regulatory cells by immature dendritic cells. J. Exp. Med. 2001. 193: F5-F9.
21. Steinman, R. M., Hawiger, D. and Nussenzweig, M. C., Tolerogenic dendritic cells. Annu. Rev. Immunol. 2003. 21: 685-711.
22. Hong, C., Kidani, Y., A-Gonzalez, N., Phung, T., Ito, A., Rong, X., Ericson, K. et al., Coordinate regulation of neutrophil homeostasis by liver X receptors in mice. J. Clin. Invest. 2012. 122: 337-347.
23. Geyeregger, R., Zeyda, M., Bauer, W., Kriehuber, E., Saemann, M. D., Zlabinger, G. J., Maurer, D. et al., Liver X receptors regulate dendritic cell phenotype and function through blocked induction of the actin-bundling protein fascin. Blood 2007. 109: 4288-4295.
24. Hanley, T. M., Blay Puryear, W., Gummuluru, S. and Viglianti, G. A., PPARgamma and LXR signaling inhibit dendritic cell-mediated hiv-1 capture and trans-infection. PLoS Pathog. 2010. 6: E1000981.
25. Bruckner, M., Dickel, D., Singer, E. and Legler, D. F., Converse regulation of CCR7-driven human dendritic cell migration by Prostaglandin E(2) and liver X receptor activation. Eur. J. Immunol. 2012. 42: 2949-2958.
26. Scandella, E., Men, Y., Gillessen, S., Forster, R. and Groettrup, M., Prostaglandin E2 is a key factor for CCR7 surface expression and migration of monocyte-derived dendritic cells. Blood 2002. 100: 1354-1361.
27. Feig, J. E., Pineda-Torra, I., Sanson, M., Bradley, M. N., Vengrenyuk, Y., Bogunovic, D., Gautier, E. L. et al., LXR promotes the maximal egress of monocyte-derived cells from mouse aortic plaques during atherosclerosis regression. J. Clin. Invest. 2010. 120: 4415-4424.
28. Bensinger, S. J., Bradley, M. N., Joseph, S. B., Zelcer, N., Janssen, E. M., Hausner, M. A., Shih, R. et al., LXR signaling couples sterol metabolism to proliferation in the acquired immune response. Cell 2008. 134: 97-111.
29. Geyeregger, R., Shehata, M., Zeyda, M., Kiefer, F. W., Stuhlmeier, K. M., Porpaczy, E., Zlabinger et al., Liver X receptors interfere with cytokine-induced proliferation and cell survival in normal and leukemic lymphocytes. J. Leukoc. Biol. 2009. 86: 1039-1048.
30. Cui, G., Qin, X., Wu, L., Zhang, Y., Sheng, X., Yu, Q., Sheng, H. et al., Liver X receptor (LXR) mediates negative regulation of mouse and human Th17 differentiation. J. Clin. Invest. 2011. 121: 658-670.
31. Hannedouche, S., Zhang, J., Yi, T., Shen, W., Nguyen, D., Pereira, J. P., Guerini, D. et al., Oxysterols direct immune cell migration via EBI2. Nature 2011. 475: 524-527.
32. Liu, C., Yang, X. V., Wu, J., Kuei, C., Mani, N. S., Zhang, L., Yu, J. et al., Oxysterols direct B-cell migration through EBI2. Nature 2011. 475: 519-523.
33. Gatto, D., Wood, K., Caminschi, I., Murphy-Durland, D., Schofield, P., Christ, D., Karupiah, G. et al., The chemotactic receptor EBI2 regulates the homeostasis, localization and immunological function of splenic dendritic cells. Nat. Immunol. 2013. 14: 446-453.
34. Raccosta, L., Fontana, R., Maggioni, D., Lanterna, C., Villablanca, E. J., Paniccia, A., Musumeci, A. et al., The oxysterol-CXCR2 axis plays a key role in the recruitment of tumor-promoting neutrophils. J. Exp. Med. 2013. 210: 1711-1728.
35. Vesely, M. D., Kershaw, M. H., Schreiber, R. D. and Smyth, M. J., Natural innate and adaptive immunity to cancer. Annu. Rev. Immunol. 2011. 29: 235-271.
36. Russo, V., Metabolism, LXR/LXR ligands, and tumor immune escape. J. Leukoc. Biol. 2011. 90: 673-679.
37. Laffitte, B. A., Joseph, S. B., Walczak, R., Pei, L., Wilpitz, D. C., Collins, J. L. and Tontonoz, P., Autoregulation of the human liver X receptor alpha promoter. Mol. Cell Biol. 2001. 21: 7558-7568.
38. Randolph, G. J., Ochando, J. and Partida-Sanchez, S., Migration of dendritic cell subsets and their precursors. Annu. Rev. Immunol. 2008. 26: 293-316.
39. Sallusto, F., Mackay, C. R. and Lanzavecchia, A., The role of chemokine receptors in primary, effector, and memory immune responses. Annu. Rev. Immunol. 2000. 18: 593-620.
40. Steinman, R. M., Turley, S., Mellman, I. and Inaba, K., The induction of tolerance by dendritic cells that have captured apoptotic cells. J. Exp. Med. 2000. 191: 411-416.
41. Jakobsson, T., Treuter, E., Gustafsson, J. A. and Steffensen, K. R., Liver X receptor biology and pharmacology: new pathways, challenges and opportunities. Trends Pharmacol. Sci. 2012. 33: 394-404.
42. Mantovani, A., Cassatella, M. A., Costantini, C. and Jaillon, S., Neutrophils in the activation and regulation of innate and adaptive immunity. Nat. Rev. Immunol. 2011. 11: 519-531.
43. Dunn, S. E., Youssef, S., Goldstein, M. J., Prod'homme, T., Weber, M. S., Zamvil, S. S. and Steinman, L., Isoprenoids determine Th1/Th2 fate in pathogenic T cells, providing a mechanism of modulation of autoimmunity by atorvastatin. J. Exp. Med. 2006. 203: 401-412.
44. Greenwood, J., Steinman, L. and Zamvil, S. S., Statin therapy and autoimmune disease: from protein prenylation to immunomodulation. Nat. Rev. Immunol. 2006. 6: 358-370.
45. Pardoll, D. M., The blockade of immune checkpoints in cancer immunotherapy. Nat. Rev. Cancer 2012. 12: 252-264.
46. Vedin, L. L., Lewandowski, S. A., Parini, P., Gustafsson, J. A. and Steffensen, K. R., The oxysterol receptor LXR inhibits proliferation of human breast cancer cells. Carcinogenesis 2009. 30: 575-579.
47. Vedin, L. L., Gustafsson, J. A. and Steffensen, K. R., The oxysterol receptors LXRalpha and LXRbeta suppress proliferation in the colon. Mol. Carcinog. 2013. 52: 835-844.
48. Lo Sasso, G., Bovenga, F., Murzilli, S., Salvatore, L., Di Tullio, G., Martelli, N., D'Orazio, A. et al., Liver X receptors inhibit proliferation of human colorectal cancer cells and growth of intestinal tumors in mice. Gastroenterology 2013. 144: 1497-1507, 1507 E1491-1413.
49. Pommier, A. J., Dufour, J., Alves, G., Viennois, E., De Boussac, H., Trousson, A., Volle, D. H. et al., Liver X receptors protect from development of prostatic intra-epithelial neoplasia in mice. PLoS Gen. 2013. 9: E1003483.
50. Fukuchi, J., Kokontis, J. M., Hiipakka, R. A., Chuu, C. P. and Liao, S., Antiproliferative effect of liver X receptor agonists on LNCaP human prostate cancer cells. Cancer Res. 2004. 64: 7686-7689.
51. Pommier, A. J., Alves, G., Viennois, E., Bernard, S., Communal, Y., Sion, B., Marceau, G. et al., Liver X receptor activation downregulates akt survival signaling in lipid rafts and induces apoptosis of prostate cancer cells. Oncogene 2010. 29: 2712-2723.
52. Guo, D., Reinitz, F., Youssef, M., Hong, C., Nathanson, D., Akhavan, D., Kuga, D. et al., An LXR agonist promotes glioblastoma cell death through inhibition of an EGFR/AKT/SREBP-1/LDLR-dependent pathway. Cancer Discov. 2011. 1: 442-456.
53. Riobo, N. A., Cholesterol and its derivatives in sonic Hedgehog signaling and cancer. Curr. Op. Pharmacol. 2012. 12: 736-741.
54. Nachtergaele, S., Mydock, L. K., Krishnan, K., Rammohan, J., Schlesinger, P. H., Covey, D. F. and Rohatgi, R., Oxysterols are allosteric activators of the oncoprotein smoothened. Nat. Chem. Biol. 2012. 8: 211-220.
55. Corcoran, R. B. and Scott, M. P., Oxysterols stimulate sonic Hedgehog signal transduction and proliferation of medulloblastoma cells. Proc. Natl. Acad. Sci. US A 2006. 103: 8408-8413.
56. Nelson, E. R., Wardell, S. E., Jasper, J. S., Park, S., Suchindran, S., Howe, M. K., Carver, N. J. et al., 27-Hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology. Science 2013. 342: 1094-1098.