Advances of three oxysterols in inflammation and immunology_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

CAO Qin ¹ ,  YE Qifa ^1,2

1. Zhongnan Hospital of Wuhan University, Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Wuhan 430071, P. R. China;
2. The 3rd Xiangya Hospital of Central South University, Research Center of National Health Ministry on Transplantation Medicine Engineering and Technology, Changsha 410013, P. R. China;

Corresponding author：

YE Qifa, Email: yqf_china@163.com

Keywords：

oxysterols; inflammation; immunologic response; anti-virus

DOI：

10.7507/1007-9424.201901041

Video：

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Abstract Full text Figures/Tables Video References Cited by

Objective To summarize progress of 25-hydroxycholesterol (25-OHC), 27-hydroxycholesterol(27-OHC), and 7α,25-hydroxycholesterol (7α,25-OHC) three oxidized cholesterols in inflammation and immunology and to provide evidence for related basic researches and diseases treatments.Method The relevant literatures about these three important oxidized cholesterols in the inflammation and immunology in recent years were reviewed.Results The 25-OHC and 27-OHC could exert the antiviral effects by interfering with various viruses invading the host via various mechanisms. Moreover, the 25-OHC and 27-OHC also played the important regulatory roles in a variety of inflammatory processes and inflammatory diseases. The 7α,25-OHC played the important role in a variety of inflammatory processes by acting on the inflammatory and immune cell membrane receptor G-protein coupled receptor 183 (also known as Epstein-Barr virus-inducible receptor 2).Conclusion 25-OHC, 27-OHC and 7α,25-OHC play an important roles in occurrence and development of various inflammatory and immune responses and diseases of inflammatory and immune by acting on a variety of nuclear receptors and membrane receptors.

Citation： CAO Qin, YE Qifa. Advances of three oxysterols in inflammation and immunology. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2019, 26(7): 876-881. doi: 10.7507/1007-9424.201901041 Copy

1.	Mutemberezi V, Guillemot-Legris O, Muccioli GG. Oxysterols: From cholesterol metabolites to key mediators. Prog Lipid Res, 2016, 64: 152-169.
2.	Cyster JG, Dang EV, Reboldi A, et al. 25-hydroxycholesterols in innate and adaptive immunity. Nat Rev Immunol, 2014, 14(11): 731-743.
3.	Warner M, Gustafsson JA. On estrogen, cholesterol metabolism, and breast cancer. N Engl J Med, 2014, 370(6): 572-573.
4.	Stiles AR, McDonald JG, Bauman DR, et al. CYP7B1: one cytochrome P450, two human genetic diseases, and multiple physiological functions. J Biol Chem, 2009, 284(42): 28485-28489.
5.	White JM, Whittaker GR. Fusion of enveloped viruses in endosomes. Traffic, 2016, 17(6): 593-614.
6.	Simons K, Gerl MJ. Revitalizing membrane rafts: new tools and insights. Nat Rev Mol Cell Biol, 2010, 11(10): 688-699.
7.	Heaton NS, Randall G. Multifaceted roles for lipids in viral infection. Trends Microbiol, 2011, 19(7): 368-375.
8.	Rothwell C, Lebreton A, Young Ng C, et al. Cholesterol biosynthesis modulation regulates dengue viral replication. Virology, 2009, 389(1-2): 8-19.
9.	Petersen J, Drake MJ, Bruce EA, et al. The major cellular sterol regulatory pathway is required for Andes virus infection. PLoS Pathog, 2014, 10(2): e1003911.
10.	Blanc M, Hsieh WY, Robertson KA, et al. Host defense against viral infection involves interferon mediated down-regulation of sterol biosynthesis. PLoS Biol, 2011, 9(3): e1000598.
11.	Civra A, Francese R, Gamba P, et al. 25-hydroxycholesterol and 27-hydroxycholesterol inhibit human rotavirus infection by sequestering viral particles into late endosomes. Redox Biol, 2018, 19: 318-330.
12.	Cagno V, Civra A, Rossin D, et al. Inhibition of herpes simplex-1 virus replication by 25-hydroxycholesterol and 27-hydro-xycholesterol. Redox Biol, 2017, 12: 522-527.
13.	Blanc M, Hsieh WY, Robertson KA, et al. The transcription factor STAT-1 couples macrophage synthesis of 25-hydroxycholesterol to the interferon antiviral response. Immunity, 2013, 38(1): 106-118.
14.	Shibata N, Carlin AF, Spann NJ, et al. 25-hydroxycholesterol activates the integrated stress response to reprogram transcription and translation in macrophages. J Biol Chem, 2013, 288(50): 35812-35823.
15.	Liu SY, Sanchez DJ, Aliyari R, et al. Systematic identification of type Ⅰ and type Ⅱ interferon-induced antiviral factors. Proc Natl Acad Sci U S A, 2012, 109(11): 4239-4244.
16.	Mboko WP, Mounce BC, Emmer J, et al. Interferon regulatory factor 1 restricts gamma herpesvirus replication in primary immune cells. J Virol, 2014, 88(12): 6993-7004.
17.	Anggakusuma, Romero-Brey I, Berger C, et al. Interferon-inducible cholesterol-25-hydroxylase restricts hepatitis C virus replication through blockage of membranous web formation. Hepatology, 2015, 62(3): 702-714.
18.	Li C, Deng YQ, Wang S, et al. 25-hydroxycholesterol protects host against Zika virus infection and its associated microcephaly in a mouse model. Immunity, 2017, 46(3): 446-456.
19.	Wang J, Zeng L, Zhang L, et al. Cholesterol 25-hydroxylase acts as a host restriction factor on pseudorabies virus replication. J Gen Virol, 2017, 98(6): 1467-1476.
20.	Ke W, Fang L, Jing H, et al. Cholesterol 25-hydroxylase inhibits porcine reproductive and respiratory syndrome virus replication through enzyme activity-dependent and -independent mechanisms. J Virol, 2017, 91(19). pii: 827-817.
21.	Doms A, Sanabria T, Hansen JN, et al. 25-hydroxycholesterol production by the cholesterol-25-hydroxylase interferon-stimulated gene restricts mammalian reovirus infection. J Virol, 2018, 92(18). pii: 1047-1018.
22.	You H, Yuan H, Fu W, et al. Herpes simplex virus type 1 abrogates the antiviral activity of CH25H via its virion host shutoff protein. Antiviral Res, 2017, 143: 69-73.
23.	Dong H, Zhou L, Ge X, et al. Porcine reproductive and respiratory syndrome virus nsp1β and nsp11 antagonize the antiviral activity of cholesterol-25-hydroxylase via lysosomal degradation. Vet Microbiol, 2018, 223: 134-143.
24.	Shrivastava-Ranjan P, Bergeron É, Chakrabarti AK, et al. 25-Hydroxycholesterol inhibition of Lassa virus infection through aberrant GP1 glycosylation. MBio, 2016, 7(6). pii: 1808-1816.
25.	Liu SY, Aliyari R, Chikere K, et al. Interferon-inducible cholesterol-25-hydroxylase broadly inhibits viral entry by production of 25-hydroxycholesterol. Immunity, 2013, 38(1): 92-105.
26.	Song Z, Zhang Q, Liu X, et al. Cholesterol 25-hydroxylase is an interferon-inducible factor that protects against porcine reproductive and respiratory syndrome virus infection. Vet Microbiol, 2017, 210: 153-161.
27.	Arita M, Kojima H, Nagano T, et al. Oxysterol-binding protein family Ⅰ is the target of minor enviroxime-like compounds. J Virol, 2013, 87(8): 4252-4260.
28.	Burke ML, McGarvey L, McSorley HJ, et al. Migrating Schistosoma japonicum schistosomula induce an innate immune response and wound healing in the murine lung. Mol Immunol, 2011, 49(1-2): 191-200.
29.	Tuong ZK, Lau P, Yeo JC, et al. Disruption of Rorα1 and cholesterol 25-hydroxylase expression attenuates phagocytosis in male Rorα^sg/sg mice. Endocrinology, 2013, 154(1): 140-149.
30.	Reboldi A, Dang EV, McDonald JG, et al. Inflammation. 25-hydroxycholesterol suppresses interleukin-1-driven inflammation downstream of type Ⅰ interferon. Science, 2014, 345(6197): 679-684.
31.	Vigne S, Chalmin F, Duc D, et al. IL-27-induced type 1 regulatory T-cells produce oxysterols that constrain IL-10 production. Front Immunol, 2017, 8: 1184.
32.	Viaud M, Ivanov S, Vujic N, et al. Lysosomal cholesterol hydrolysis couples efferocytosis to anti-inflammatory oxysterol production. Circ Res, 2018, 122(10): 1369-1384.
33.	Dang EV, McDonald JG, Russell DW, et al. Oxysterol restraint of cholesterol synthesis prevents AIM2 inflammasome activation. Cell, 2017, 171(5): 1057-1071.
34.	Gold ES, Diercks AH, Podolsky I, et al. 25-hydroxycholesterol acts as an amplifier of inflammatory signaling. Proc Natl Acad Sci U S A, 2014, 111(29): 10666-10671.
35.	Jang J, Park S, Jin Hur H, et al. 25-hydroxycholesterol contributes to cerebral inflammation of X-linked adrenoleukodystrophy through activation of the NLRP3 inflammasome. Nat Commun, 2016, 7: 13129.
36.	Umetani M, Ghosh P, Ishikawa T, et al. The cholesterol metabolite 27-hydroxycholesterol promotes atherosclerosis via proinflammatory processes mediated by estrogen receptor alpha. Cell Metab, 2014, 20(1): 172-182.
37.	Bieghs V, Hendrikx T, van Gorp PJ, et al. The cholesterol derivative 27-hydroxycholesterol reduces steatohepatitis in mice. Gastroenterology, 2013, 144(1): 167-178.
38.	Testa G, Staurenghi E, Zerbinati C, et al. Changes in brain oxysterols at different stages of Alzheimer’s disease: Their involvement in neuroinflammation. Redox Biol, 2016, 10: 24-33.
39.	Nelson ER, Wardell SE, Jasper JS, et al. 27-hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology. Science, 2013, 342(6162): 1094-1098.
40.	Umetani M, Domoto H, Gormley AK, et al. 27-hydroxycholesterol is an endogenous SERM that inhibits the cardiovascular effects of estrogen. Nat Med, 2007, 13(10): 1185-1192.
41.	Umetani M, Shaul PW. 27-hydroxycholesterol: the first identified endogenous SERM. Trends Endocrinol Metab, 2011, 22(4): 130-135.
42.	Gargiulo S, Gamba P, Testa G, et al. Relation between TLR4/NF-κB signaling pathway activation by 27-hydroxycholesterol and 4-hydroxynonenal, and atherosclerotic plaque instability. Aging Cell, 2015, 14(4): 569-581.
43.	Gargiulo S, Rossin D, Testa G, et al. Up-regulation of COX-2 and mPGES-1 by 27-hydroxycholesterol and 4-hydroxynonenal: A crucial role in atherosclerotic plaque instability. Free Radic Biol Med, 2018, 129: 354-363.
44.	Hendrikx T, Jeurissen ML, Bieghs V, et al. Hematopoietic overexpression of Cyp27a1 reduces hepatic inflammation independently of 27-hydroxycholesterol levels in Ldlr^-/- mice. J Hepatol, 2015, 62(2): 430-436.
45.	Pereira JP, Kelly LM, Xu Y, et al. EBI2 mediates B cell segregation between the outer and centre follicle. Nature, 2009, 460(7259): 1122-1126.
46.	Gatto D, Paus D, Basten A, et al. Guidance of B cells by the orphan G protein-coupled receptor EBI2 shapes humoral immune responses. Immunity, 2009, 31(2): 259-269.
47.	Liu C, Yang XV, Wu J, et al. Oxysterols direct B-cell migration through EBI2. Nature, 2011, 475(7357): 519-523.
48.	Hannedouche S, Zhang J, Yi T, et al. Oxysterols direct immune cell migration via EBI2. Nature, 2011, 475(7357): 524-527.
49.	Yi T, Wang X, Kelly LM, et al. Oxysterol gradient generation by lymphoid stromal cells guides activated B cell movement during humoral responses. Immunity, 2012, 37(3): 535-548.
50.	Gatto D, Wood K, Caminschi I, et al. The chemotactic receptor EBI2 regulates the homeostasis, localization and immunological function of splenic dendritic cells. Nat Immunol, 2013, 14(5): 446-453.
51.	Yi T, Cyster JG. EBI2-mediated bridging channel positioning supports splenic dendritic cell homeostasis and particulate antigen capture. Elife, 2013, 2: e00757.
52.	Li J, Lu E, Yi T, et al. EBI2 augments Tfh cell fate by promoting interaction with IL-2-quenching dendritic cells. Nature, 2016, 533(7601): 110-114.
53.	Chalmin F, Rochemont V, Lippens C, et al. Oxysterols regulate encephalitogenic CD4⁺ T cell trafficking during central nervous system autoimmunity. J Autoimmun, 2015, 56: 45-55.
54.	Wanke F, Moos S, Croxford AL, et al. EBI2 is highly expressed in multiple sclerosis lesions and promotes early CNS migration of encephalitogenic CD4 T cells. Cell Rep, 2017, 18(5): 1270-1284.
55.	Wanke F, Croxford AL, Heinena AP, et al. Expression of the G-protein coupled receptor EBI2 in T cells is highly regulated and confers pathogenicity to myelin specific Th17 cells. J Neuroimmunol, 2014, 275(1): 211.
56.	Niss Arfelt K, Barington L, Benned-Jensen T, et al. EBI2 overexpression in mice leads to B1 B-cell expansion and chronic lymphocytic leukemia-like B-cell malignancies. Blood, 2017, 129(7): 866-878.
57.	Shen ZJ, Hu J, Kashi VP, et al. Epstein-Barr virus-induced gene 2 mediates allergen-induced leukocyte migration into airways. Am J Respir Crit Care Med, 2017, 195(12): 1576-1585.
58.	Rutkowska A, Sailer AW, Dev KK. EBI2 receptor regulates myelin development and inhibits LPC-induced demyelination. J Neuroinflammation, 2017, 14(1): 250.
59.	Chu C, Moriyama S, Li Z, et al. Anti-microbial functions of group 3 innate lymphoid cells in gut-associated lymphoid tissues are regulated by G-protein-coupled receptor 183. Cell Rep, 2018, 23(13): 3750-3758.
60.	Emgård J, Kammoun H, García-Cassani B, et al. Oxysterol sensing through the receptor GPR183 promotes the lymphoid-tissue-inducing function of innate lymphoid cells and colonic inflammation. Immunity, 2018, 48(1): 120-132.
61.	Jia J, Conlon TM, Sarker RS, et al. Cholesterol metabolism promotes B-cell positioning during immune pathogenesis of chronic obstructive pulmonary disease. EMBO Mol Med, 2018, 10(5). pii: e8349.
62.	Rutkowska A, Shimshek DR, Sailer AW, et al. EBI2 regulates pro-inflammatory signalling and cytokine release in astrocytes. Neuropharmacology, 2018, 133: 121-128.

1. Mutemberezi V, Guillemot-Legris O, Muccioli GG. Oxysterols: From cholesterol metabolites to key mediators. Prog Lipid Res, 2016, 64: 152-169.
2. Cyster JG, Dang EV, Reboldi A, et al. 25-hydroxycholesterols in innate and adaptive immunity. Nat Rev Immunol, 2014, 14(11): 731-743.
3. Warner M, Gustafsson JA. On estrogen, cholesterol metabolism, and breast cancer. N Engl J Med, 2014, 370(6): 572-573.
4. Stiles AR, McDonald JG, Bauman DR, et al. CYP7B1: one cytochrome P450, two human genetic diseases, and multiple physiological functions. J Biol Chem, 2009, 284(42): 28485-28489.
5. White JM, Whittaker GR. Fusion of enveloped viruses in endosomes. Traffic, 2016, 17(6): 593-614.
6. Simons K, Gerl MJ. Revitalizing membrane rafts: new tools and insights. Nat Rev Mol Cell Biol, 2010, 11(10): 688-699.
7. Heaton NS, Randall G. Multifaceted roles for lipids in viral infection. Trends Microbiol, 2011, 19(7): 368-375.
8. Rothwell C, Lebreton A, Young Ng C, et al. Cholesterol biosynthesis modulation regulates dengue viral replication. Virology, 2009, 389(1-2): 8-19.
9. Petersen J, Drake MJ, Bruce EA, et al. The major cellular sterol regulatory pathway is required for Andes virus infection. PLoS Pathog, 2014, 10(2): e1003911.
10. Blanc M, Hsieh WY, Robertson KA, et al. Host defense against viral infection involves interferon mediated down-regulation of sterol biosynthesis. PLoS Biol, 2011, 9(3): e1000598.
11. Civra A, Francese R, Gamba P, et al. 25-hydroxycholesterol and 27-hydroxycholesterol inhibit human rotavirus infection by sequestering viral particles into late endosomes. Redox Biol, 2018, 19: 318-330.
12. Cagno V, Civra A, Rossin D, et al. Inhibition of herpes simplex-1 virus replication by 25-hydroxycholesterol and 27-hydro-xycholesterol. Redox Biol, 2017, 12: 522-527.
13. Blanc M, Hsieh WY, Robertson KA, et al. The transcription factor STAT-1 couples macrophage synthesis of 25-hydroxycholesterol to the interferon antiviral response. Immunity, 2013, 38(1): 106-118.
14. Shibata N, Carlin AF, Spann NJ, et al. 25-hydroxycholesterol activates the integrated stress response to reprogram transcription and translation in macrophages. J Biol Chem, 2013, 288(50): 35812-35823.
15. Liu SY, Sanchez DJ, Aliyari R, et al. Systematic identification of type Ⅰ and type Ⅱ interferon-induced antiviral factors. Proc Natl Acad Sci U S A, 2012, 109(11): 4239-4244.
16. Mboko WP, Mounce BC, Emmer J, et al. Interferon regulatory factor 1 restricts gamma herpesvirus replication in primary immune cells. J Virol, 2014, 88(12): 6993-7004.
17. Anggakusuma, Romero-Brey I, Berger C, et al. Interferon-inducible cholesterol-25-hydroxylase restricts hepatitis C virus replication through blockage of membranous web formation. Hepatology, 2015, 62(3): 702-714.
18. Li C, Deng YQ, Wang S, et al. 25-hydroxycholesterol protects host against Zika virus infection and its associated microcephaly in a mouse model. Immunity, 2017, 46(3): 446-456.
19. Wang J, Zeng L, Zhang L, et al. Cholesterol 25-hydroxylase acts as a host restriction factor on pseudorabies virus replication. J Gen Virol, 2017, 98(6): 1467-1476.
20. Ke W, Fang L, Jing H, et al. Cholesterol 25-hydroxylase inhibits porcine reproductive and respiratory syndrome virus replication through enzyme activity-dependent and -independent mechanisms. J Virol, 2017, 91(19). pii: 827-817.
21. Doms A, Sanabria T, Hansen JN, et al. 25-hydroxycholesterol production by the cholesterol-25-hydroxylase interferon-stimulated gene restricts mammalian reovirus infection. J Virol, 2018, 92(18). pii: 1047-1018.
22. You H, Yuan H, Fu W, et al. Herpes simplex virus type 1 abrogates the antiviral activity of CH25H via its virion host shutoff protein. Antiviral Res, 2017, 143: 69-73.
23. Dong H, Zhou L, Ge X, et al. Porcine reproductive and respiratory syndrome virus nsp1β and nsp11 antagonize the antiviral activity of cholesterol-25-hydroxylase via lysosomal degradation. Vet Microbiol, 2018, 223: 134-143.
24. Shrivastava-Ranjan P, Bergeron É, Chakrabarti AK, et al. 25-Hydroxycholesterol inhibition of Lassa virus infection through aberrant GP1 glycosylation. MBio, 2016, 7(6). pii: 1808-1816.
25. Liu SY, Aliyari R, Chikere K, et al. Interferon-inducible cholesterol-25-hydroxylase broadly inhibits viral entry by production of 25-hydroxycholesterol. Immunity, 2013, 38(1): 92-105.
26. Song Z, Zhang Q, Liu X, et al. Cholesterol 25-hydroxylase is an interferon-inducible factor that protects against porcine reproductive and respiratory syndrome virus infection. Vet Microbiol, 2017, 210: 153-161.
27. Arita M, Kojima H, Nagano T, et al. Oxysterol-binding protein family Ⅰ is the target of minor enviroxime-like compounds. J Virol, 2013, 87(8): 4252-4260.
28. Burke ML, McGarvey L, McSorley HJ, et al. Migrating Schistosoma japonicum schistosomula induce an innate immune response and wound healing in the murine lung. Mol Immunol, 2011, 49(1-2): 191-200.
29. Tuong ZK, Lau P, Yeo JC, et al. Disruption of Rorα1 and cholesterol 25-hydroxylase expression attenuates phagocytosis in male Rorα^sg/sg mice. Endocrinology, 2013, 154(1): 140-149.
30. Reboldi A, Dang EV, McDonald JG, et al. Inflammation. 25-hydroxycholesterol suppresses interleukin-1-driven inflammation downstream of type Ⅰ interferon. Science, 2014, 345(6197): 679-684.
31. Vigne S, Chalmin F, Duc D, et al. IL-27-induced type 1 regulatory T-cells produce oxysterols that constrain IL-10 production. Front Immunol, 2017, 8: 1184.
32. Viaud M, Ivanov S, Vujic N, et al. Lysosomal cholesterol hydrolysis couples efferocytosis to anti-inflammatory oxysterol production. Circ Res, 2018, 122(10): 1369-1384.
33. Dang EV, McDonald JG, Russell DW, et al. Oxysterol restraint of cholesterol synthesis prevents AIM2 inflammasome activation. Cell, 2017, 171(5): 1057-1071.
34. Gold ES, Diercks AH, Podolsky I, et al. 25-hydroxycholesterol acts as an amplifier of inflammatory signaling. Proc Natl Acad Sci U S A, 2014, 111(29): 10666-10671.
35. Jang J, Park S, Jin Hur H, et al. 25-hydroxycholesterol contributes to cerebral inflammation of X-linked adrenoleukodystrophy through activation of the NLRP3 inflammasome. Nat Commun, 2016, 7: 13129.
36. Umetani M, Ghosh P, Ishikawa T, et al. The cholesterol metabolite 27-hydroxycholesterol promotes atherosclerosis via proinflammatory processes mediated by estrogen receptor alpha. Cell Metab, 2014, 20(1): 172-182.
37. Bieghs V, Hendrikx T, van Gorp PJ, et al. The cholesterol derivative 27-hydroxycholesterol reduces steatohepatitis in mice. Gastroenterology, 2013, 144(1): 167-178.
38. Testa G, Staurenghi E, Zerbinati C, et al. Changes in brain oxysterols at different stages of Alzheimer’s disease: Their involvement in neuroinflammation. Redox Biol, 2016, 10: 24-33.
39. Nelson ER, Wardell SE, Jasper JS, et al. 27-hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology. Science, 2013, 342(6162): 1094-1098.
40. Umetani M, Domoto H, Gormley AK, et al. 27-hydroxycholesterol is an endogenous SERM that inhibits the cardiovascular effects of estrogen. Nat Med, 2007, 13(10): 1185-1192.
41. Umetani M, Shaul PW. 27-hydroxycholesterol: the first identified endogenous SERM. Trends Endocrinol Metab, 2011, 22(4): 130-135.
42. Gargiulo S, Gamba P, Testa G, et al. Relation between TLR4/NF-κB signaling pathway activation by 27-hydroxycholesterol and 4-hydroxynonenal, and atherosclerotic plaque instability. Aging Cell, 2015, 14(4): 569-581.
43. Gargiulo S, Rossin D, Testa G, et al. Up-regulation of COX-2 and mPGES-1 by 27-hydroxycholesterol and 4-hydroxynonenal: A crucial role in atherosclerotic plaque instability. Free Radic Biol Med, 2018, 129: 354-363.
44. Hendrikx T, Jeurissen ML, Bieghs V, et al. Hematopoietic overexpression of Cyp27a1 reduces hepatic inflammation independently of 27-hydroxycholesterol levels in Ldlr^-/- mice. J Hepatol, 2015, 62(2): 430-436.
45. Pereira JP, Kelly LM, Xu Y, et al. EBI2 mediates B cell segregation between the outer and centre follicle. Nature, 2009, 460(7259): 1122-1126.
46. Gatto D, Paus D, Basten A, et al. Guidance of B cells by the orphan G protein-coupled receptor EBI2 shapes humoral immune responses. Immunity, 2009, 31(2): 259-269.
47. Liu C, Yang XV, Wu J, et al. Oxysterols direct B-cell migration through EBI2. Nature, 2011, 475(7357): 519-523.
48. Hannedouche S, Zhang J, Yi T, et al. Oxysterols direct immune cell migration via EBI2. Nature, 2011, 475(7357): 524-527.
49. Yi T, Wang X, Kelly LM, et al. Oxysterol gradient generation by lymphoid stromal cells guides activated B cell movement during humoral responses. Immunity, 2012, 37(3): 535-548.
50. Gatto D, Wood K, Caminschi I, et al. The chemotactic receptor EBI2 regulates the homeostasis, localization and immunological function of splenic dendritic cells. Nat Immunol, 2013, 14(5): 446-453.
51. Yi T, Cyster JG. EBI2-mediated bridging channel positioning supports splenic dendritic cell homeostasis and particulate antigen capture. Elife, 2013, 2: e00757.
52. Li J, Lu E, Yi T, et al. EBI2 augments Tfh cell fate by promoting interaction with IL-2-quenching dendritic cells. Nature, 2016, 533(7601): 110-114.
53. Chalmin F, Rochemont V, Lippens C, et al. Oxysterols regulate encephalitogenic CD4⁺ T cell trafficking during central nervous system autoimmunity. J Autoimmun, 2015, 56: 45-55.
54. Wanke F, Moos S, Croxford AL, et al. EBI2 is highly expressed in multiple sclerosis lesions and promotes early CNS migration of encephalitogenic CD4 T cells. Cell Rep, 2017, 18(5): 1270-1284.
55. Wanke F, Croxford AL, Heinena AP, et al. Expression of the G-protein coupled receptor EBI2 in T cells is highly regulated and confers pathogenicity to myelin specific Th17 cells. J Neuroimmunol, 2014, 275(1): 211.
56. Niss Arfelt K, Barington L, Benned-Jensen T, et al. EBI2 overexpression in mice leads to B1 B-cell expansion and chronic lymphocytic leukemia-like B-cell malignancies. Blood, 2017, 129(7): 866-878.
57. Shen ZJ, Hu J, Kashi VP, et al. Epstein-Barr virus-induced gene 2 mediates allergen-induced leukocyte migration into airways. Am J Respir Crit Care Med, 2017, 195(12): 1576-1585.
58. Rutkowska A, Sailer AW, Dev KK. EBI2 receptor regulates myelin development and inhibits LPC-induced demyelination. J Neuroinflammation, 2017, 14(1): 250.
59. Chu C, Moriyama S, Li Z, et al. Anti-microbial functions of group 3 innate lymphoid cells in gut-associated lymphoid tissues are regulated by G-protein-coupled receptor 183. Cell Rep, 2018, 23(13): 3750-3758.
60. Emgård J, Kammoun H, García-Cassani B, et al. Oxysterol sensing through the receptor GPR183 promotes the lymphoid-tissue-inducing function of innate lymphoid cells and colonic inflammation. Immunity, 2018, 48(1): 120-132.
61. Jia J, Conlon TM, Sarker RS, et al. Cholesterol metabolism promotes B-cell positioning during immune pathogenesis of chronic obstructive pulmonary disease. EMBO Mol Med, 2018, 10(5). pii: e8349.
62. Rutkowska A, Shimshek DR, Sailer AW, et al. EBI2 regulates pro-inflammatory signalling and cytokine release in astrocytes. Neuropharmacology, 2018, 133: 121-128.

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Advances of three oxysterols in inflammation and immunology

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