The cholesterol biosynthesis pathway regulates IL-10 expression in human Th1 cells

Nature Communications

Volumn 10, Issue 1, 2019, Pages

  Perucha, Esperanza ^a,b   Melchiotti, Rossella ^c   Bibby, Jack A ^a,b   Wu, Wing ^a,b   Frederiksen, Klaus Stensgaard ^d   Roberts, Ceri A ^b,k   Hall, Zoe ^e   LeFriec, Gaelle ^a   Robertson, Kevin A ^f   Lavender, Paul ^a   Gerwien, Jens Gammeltoft ^d,l   Taams, Leonie S ^b   Griffin, Julian L ^e   de Rinaldis, Emanuele ^c   van Baarsen, Lisa G M ^g   Kemper, Claudia ^a,h,i   Ghazal, Peter ^f,j   Cope, Andrew P ^a,b  

^a KING'S COLLEGE LONDON   (United Kingdom)

^b KING'S COLLEGE LONDON   (United Kingdom)

^c GUY'S AND ST THOMAS' NHS FOUNDATION TRUST   (United Kingdom)

^d NOVO NORDISK A S   (Denmark)

^e UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^f UNIVERSITY OF EDINBURGH   (United Kingdom)

^g UNIVERSITY OF AMSTERDAM   (Netherlands)

^h NATIONAL HEART LUNG AND BLOOD INSTITUTE   (United States)

ⁱ UNIVERSITY OF LÜBECK   (Germany)

^j CARDIFF UNIVERSITY   (United Kingdom)

^k NHS BLOOD AND TRANSPLANT   (United Kingdom)

^l Eli Lilly   (Denmark)

more..

Author keywords

[No Author keywords available]

Indexed keywords

25 HYDROXYCHOLESTEROL; ATORVASTATIN; COLECALCIFEROL; CYTOKINE; GAMMA INTERFERON; INTERLEUKIN 10; MEVALONIC ACID; TRANSCRIPTION FACTOR C MAF; 25-HYDROXYCHOLESTEROL; CHOLESTEROL; CHOLESTEROL DERIVATIVE; IL10 PROTEIN, HUMAN;

ARTICLE; CHOLESTEROL METABOLISM; CHOLESTEROL SYNTHESIS; GENE EXPRESSION; HUMAN; HUMAN CELL; ISOPRENYLATION; JOINT BIOPSY; PREDICTIVE VALUE; REGULATORY MECHANISM; STEROL METABOLISM; T LYMPHOCYTE; TH1 CELL; TRANSCRIPTION REGULATION; BIOSYNTHESIS; DRUG EFFECT; METABOLISM;

ATORVASTATIN; CHOLESTEROL; HUMANS; HYDROXYCHOLESTEROLS; INTERFERON-GAMMA; INTERLEUKIN-10; TH1 CELLS;

EID: 85060943397     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/s41467-019-08332-9     Document Type: Article

References (66)

1. Abbas, A. K., Murphy, K. M. & Sher, A. Functional diversity of helper T lymphocytes. Nature 383, 787–793 (1996)
2. O’Garra, A. & Vieira, P. T(H)1 cells control themselves by producing interleukin-10. Nat. Rev. Immunol. 7, 425–428 (2007)
3. Dalton, D. K. et al. Multiple defects of immune cell function in mice with disrupted interferon-gamma genes. Science 259, 1739–1742 (1993)
4. de Vor, I. C. et al. Deletion of the entire interferon-gamma receptor 1 gene causing complete deficiency in three related patients. J. Clin. Immunol. 36, 195–203 (2016)
5. Cope, A., Le Friec, G., Cardone, J. & Kemper, C. The Th1 life cycle: molecular control of IFN-gamma to IL-10 switching. Trends Immunol. 32, 278–286 (2011)
6. Gabrysova, L. et al. Negative feedback control of the autoimmune response through antigen-induced differentiation of IL-10-secreting Th1 cells. J. Exp. Med. 206, 1755–1767 (2009)
7. Jankovic, D. et al. Conventional T-bet(+)Foxp3(−) Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection. J. Exp. Med. 204, 273–283 (2007)
8. Kuhn, R., Lohler, J., Rennick, D., Rajewsky, K. & Muller, W. Interleukin-10-deficient mice develop chronic enterocolitis. Cell 75, 263–274 (1993)
9. Franke, A. et al. Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility. Nat. Genet. 40, 1319–1323 (2008)
10. Saraiva, M. et al. Interleukin-10 production by Th1 cells requires interleukin-12-induced STAT4 transcription factor and ERK MAP kinase activation by high antigen dose. Immunity 31, 209–219 (2009)
11. Pot, C. et al. Cutting edge: IL-27 induces the transcription factor c-Maf, cytokine IL-21, and the costimulatory receptor ICOS that coordinately act together to promote differentiation of IL-10-producing Tr1 cells. J. Immunol. 183, 797–801 (2009)
12. Corre, B. et al. Type I interferon potentiates T-cell receptor mediated induction of IL-10-producing CD4(+) T cells. Eur. J. Immunol. 43, 2730–2740 (2013)
13. Cao, S., Liu, J., Song, L. & Ma, X. The protooncogene c-Maf is an essential transcription factor for IL-10 gene expression in macrophages. J. Immunol. 174, 3484–3492 (2005)
14. Xu, J. et al. c-Maf regulates IL-10 expression during Th17 polarization. J. Immunol. 182, 6226–6236 (2009)
15. Apetoh, L. et al. The aryl hydrocarbon receptor interacts with c-Maf to promote the differentiation of type 1 regulatory T cells induced by IL-27. Nat. Immunol. 11, 854–861 (2010)
16. Neumann, C. et al. Role of Blimp-1 in programing Th effector cells into IL-10 producers. J. Exp. Med. 211, 1807–1819 (2014)
17. Gabrysova, L. et al. c-Maf controls immune responses by regulating disease-specific gene networks and repressing IL-2 in CD4(+) T cells. Nat. Immunol. 19, 497–507 (2018)
18. Cardone, J. et al. Complement regulator CD46 temporally regulates cytokine production by conventional and unconventional T cells. Nat. Immunol. 11, 862–871 (2010)
19. Le Friec, G. et al. The CD46-Jagged1 interaction is critical for human TH1 immunity. Nat. Immunol. 13, 1213–1221 (2012)
20. Astier, A. L., Meiffren, G., Freeman, S. & Hafler, D. A. Alterations in CD46-mediated Tr1 regulatory T cells in patients with multiple sclerosis. J. Clin. Invest. 116, 3252–3257 (2006)
21. Man, K. & Kallies, A. Synchronizing transcriptional control of T cell metabolism and function. Nat. Rev. Immunol. 15, 574–584 (2015)
22. Kolev, M. et al. Complement regulates nutrient influx and metabolic reprogramming during Th1 cell responses. Immunity 42, 1033–1047 (2015)
23. Pollizzi, K. N. & Powell, J. D. Integrating canonical and metabolic signalling programmes in the regulation of T cell responses. Nat. Rev. Immunol. 14, 435–446 (2014)
24. Thurnher, M. & Gruenbacher, G. T lymphocyte regulation by mevalonate metabolism. Sci. Signal. 8, re4 (2015)
25. Bensinger, S. J. et al. LXR signaling couples sterol metabolism to proliferation in the acquired immune response. Cell 134, 97–111 (2008)
26. Kidani, Y. et al. Sterol regulatory element-binding proteins are essential for the metabolic programming of effector T cells and adaptive immunity. Nat. Immunol. 14, 489–499 (2013)
27. Zeng, H. et al. mTORC1 couples immune signals and metabolic programming to establish T(reg)-cell function. Nature 499, 485–490 (2013)
28. Barrat, F. J. et al. In vitro generation of interleukin 10-producing regulatory CD4(+) T cells is induced by immunosuppressive drugs and inhibited by T helper type 1 (Th1)- and Th2-inducing cytokines. J. Exp. Med. 195, 603–616 (2002)
29. Blanc, M. et al. The transcription factor STAT-1 couples macrophage synthesis of 25-hydroxycholesterol to the interferon antiviral response. Immunity 38, 106–118 (2013)
30. Cyster, J. G., Dang, E. V., Reboldi, A. & Yi, T. 25-Hydroxycholesterols in innate and adaptive immunity. Nat. Rev. Immunol. 14, 731–743 (2014)
31. Savouret, J. F. et al. 7-Ketocholesterol is an endogenous modulator for the arylhydrocarbon receptor. J. Biol. Chem. 276, 3054–3059 (2001)
32. Dunn, S. E. et al. Isoprenoids determine Th1/Th2 fate in pathogenic T cells, providing a mechanism of modulation of autoimmunity by atorvastatin. J. Exp. Med. 203, 401–412 (2006)
33. Blank, N. et al. Atorvastatin inhibits T cell activation through 3-hydroxy-3-methylglutaryl coenzyme A reductase without decreasing cholesterol synthesis. J. Immunol. 179, 3613–3621 (2007)
34. Evans, H. G. et al. TNF-alpha blockade induces IL-10 expression in human CD4+ T cells. Nat. Commun. 5, 3199 (2014)
35. Roberts, C. A., Durham, L. E., Fleskens, V., Evans, H. G. & Taams, L. S. TNF blockade maintains an IL-10(+) phenotype in human effector CD4(+) and CD8(+) T cells. Front. Immunol. 8, 157 (2017)
36. Brown, M. et al. The differential effects of statins on the metastatic behaviour of prostate cancer. Br. J. Cancer 106, 1689–1696 (2012)
37. Stancu, C. & Sima, A. Statins: mechanism of action and effects. J. Cell. Mol. Med. 5, 378–387 (2001)
38. Lu F. et al. Identification of NPC1 as the target of U18666A, an inhibitor of lysosomal cholesterol export and Ebola infection. eLife 4, e12177 (2015)
39. Watterson, S. et al. A model of flux regulation in the cholesterol biosynthesis pathway: immune mediated graduated flux reduction versus statin-like led stepped flux reduction. Biochimie 95, 613–621 (2013)
40. Saraiva, M. & O’Garra, A. The regulation of IL-10 production by immune cells. Nat. Rev. Immunol. 10, 170–181 (2010)
41. Vigne, S. et al. IL-27-induced type 1 regulatory T-cells produce oxysterols that constrain IL-10 production. Front. Immunol. 8, 1184 (2017)
42. Gerlag, D. M. et al. EULAR recommendations for terminology and research in individuals at risk of rheumatoid arthritis: report from the Study Group for Risk Factors for Rheumatoid Arthritis. Ann. Rheum. Dis. 71, 638–641 (2012)
43. van Baarsen, L. et al. OP0266 Synovial tissue profiling in autoantibody positive at risk individuals reveals gene signatures associated with later development of rheumatoid arthritis. Ann. Rheum. Dis. 77, 182 (2018)
44. Chow, S. C. Immunomodulation by statins: mechanisms and potential impact on autoimmune diseases. Arch. Immunol. Ther. Exp. (Warsz.) 57, 243–251 (2009)
45. Chalubinski, M. & Broncel, M. Influence of statins on effector and regulatory immune mechanisms and their potential clinical relevance in treating autoimmune disorders. Med. Sci. Monit. 16, RA245–RA251 (2010)
46. Greenwood, J., Steinman, L. & Zamvil, S. S. Statin therapy and autoimmune disease: from protein prenylation to immunomodulation. Nat. Rev. Immunol. 6, 358–370 (2006)
47. Nath, N., Giri, S., Prasad, R., Singh, A. K. & Singh, I. Potential targets of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor for multiple sclerosis therapy. J. Immunol. 172, 1273–1286 (2004)
48. Hakamada-Taguchi, R. et al. Inhibition of hydroxymethylglutaryl-coenzyme a reductase reduces Th1 development and promotes Th2 development. Circ. Res. 93, 948–956 (2003)
49. Matsumoto, M., Einhaus, D., Gold, E. S. & Aderem, A. Simvastatin augments lipopolysaccharide-induced proinflammatory responses in macrophages by differential regulation of the c-Fos and c-Jun transcription factors. J. Immunol. 172, 7377–7384 (2004)
50. Bjarnadottir, O. et al. Global transcriptional changes following statin treatment in breast cancer. Clin. Cancer Res. 21, 3402–3411 (2015)
51. Jury, E. C., Isenberg, D. A., Mauri, C. & Ehrenstein, M. R. Atorvastatin restores Lck expression and lipid raft-associated signaling in T cells from patients with systemic lupus erythematosus. J. Immunol. 177, 7416–7422 (2006)
52. Leung, B. P. et al. A novel anti-inflammatory role for simvastatin in inflammatory arthritis. J. Immunol. 170, 1524–1530 (2003)
53. Robertson, K. A. & Ghazal, P. Interferon control of the sterol metabolic network: bidirectional molecular circuitry-mediating host protection. Front. Immunol. 7, 634 (2016)
54. Xu, M. et al. c-MAF-dependent regulatory T cells mediate immunological tolerance to a gut pathobiont. Nature 554, 373–377 (2018)
55. Radhakrishnan, S. K., den Besten, W., Deshaies, R. J. p97-dependent retrotranslocation and proteolytic processing govern formation of active Nrf1 upon proteasome inhibition. eLife 10.7554/eLife.01856 (2014)
56. Widenmaier, S. B. et al. NRF1 is an ER membrane sensor that is central to cholesterol homeostasis. Cell 171, 1094–109 e15 (2017)
57. Seo, Y. K. et al. Genome-wide localization of SREBP-2 in hepatic chromatin predicts a role in autophagy. Cell Metab. 13, 367–375 (2011)
58. Myasoedova, E. et al. Lipid paradox in rheumatoid arthritis: the impact of serum lipid measures and systemic inflammation on the risk of cardiovascular disease. Ann. Rheum. Dis. 70, 482–487 (2011)
59. Cope, A. P. et al. Chronic exposure to tumor necrosis factor (TNF) in vitro impairs the activation of T cells through the T cell receptor/CD3 complex; reversal in vivo by anti-TNF antibodies in patients with rheumatoid arthritis. J. Clin. Invest. 94, 749–760 (1994)
60. Ozen, S. & Bilginer, Y. A clinical guide to autoinflammatory diseases: familial Mediterranean fever and next-of-kin. Nat. Rev. Rheumatol. 10, 135–147 (2014)
61. van der Burgh, R., Ter Haar, N. M., Boes, M. L. & Frenkel, J. Mevalonate kinase deficiency, a metabolic autoinflammatory disease. Clin. Immunol. 147, 197–206 (2013)
62. Cheng, S. M. et al. Modulation of human T cells signaling transduction by lovastatin. Int. J. Cardiol. 140, 24–33 (2010)
63. Blanco-Colio, L. M. et al. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors decrease Fas ligand expression and cytotoxicity in activated human T lymphocytes. Circulation 108, 1506–1513 (2003)
64. Berzat, A. C., Brady, D. C., Fiordalisi, J. J. & Cox, A. D. Using inhibitors of prenylation to block localization and transforming activity. Methods Enzymol. 407, 575–597 (2006)
65. Folch, J., Lees, M. & Sloane Stanley, G. H. A simple method for the isolation and purification of total lipids from animal tissues. J. Biol. Chem. 226, 497–509 (1957)
66. Sud, M. et al. LMSD: lipid maps structure database. Nucleic Acids Res. 35, D527–D532 (2007)