TPL-2 Regulates Macrophage Lipid Metabolism and M2 Differentiation to Control TH2-Mediated Immunopathology

PLoS Pathogens

Volumn 12, Issue 8, 2016, Pages

  Kannan, Yashaswini ^a   Perez Lloret, Jimena ^a   Li, Yanda ^a   Entwistle, Lewis J ^a   Khoury, Hania ^a   Papoutsopoulou, Stamatia ^a,d   Mahmood, Radma ^a   Mansour, Nuha R ^b   Ching Cheng Huang, Stanley ^c   Pearce, Edward J ^c,e   Pedro S de Carvalho, Luiz ^a   Ley, Steven C ^a   Wilson, Mark S ^a  

^a THE FRANCIS CRICK INSTITUTE   (United Kingdom)

^b LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE   (United Kingdom)

^c WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d UNIVERSITY OF MANCHESTER   (United Kingdom)

^e UNIVERSITY OF FREIBURG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

MITOGEN ACTIVATED PROTEIN KINASE 3; PROTEIN TPL 2; UNCLASSIFIED DRUG; MAP3K8 PROTEIN, MOUSE; MITOGEN ACTIVATED PROTEIN KINASE KINASE KINASE; ONCOPROTEIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BONE MARROW CELL; CD4+ T LYMPHOCYTE; CELL DIFFERENTIATION; CONTROLLED STUDY; ENZYME LINKED IMMUNOSORBENT ASSAY; FLOW CYTOMETRY; IMMUNE RESPONSE; IMMUNOPATHOLOGY; IMMUNOREGULATION; LIPID METABOLISM; LIQUID CHROMATOGRAPHY; LIVER FIBROSIS; MACROPHAGE; MACROPHAGE ACTIVATION; MASS SPECTROMETRY; MICROARRAY ANALYSIS; MOUSE; NONHUMAN; PROTEIN EXPRESSION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SCHISTOSOMA MANSONI; SCHISTOSOMIASIS MANSONI; WESTERN BLOTTING; ANIMAL; FIBROSIS; GENETICS; IMMUNOLOGY; INFLAMMATION; KNOCKOUT MOUSE; LIPOLYSIS; PATHOLOGY; TH2 CELL;

ANIMALS; CELL DIFFERENTIATION; FIBROSIS; INFLAMMATION; LIPOLYSIS; MACROPHAGES; MAP KINASE KINASE KINASES; MICE; MICE, KNOCKOUT; PROTO-ONCOGENE PROTEINS; SCHISTOSOMA MANSONI; SCHISTOSOMIASIS MANSONI; TH2 CELLS;

EID: 84984801384     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1005783     Document Type: Article

References (71)

1. Gantke T, Sriskantharajah S, Sadowski M, Ley SC, IkappaB kinase regulation of the TPL-2/ERK MAPK pathway. Immunol Rev. 2012;246(1):168–82. doi: 10.1111/j.1600-065X.2012.01104.x22435554.
2. George D, Salmeron A, Cot/Tpl-2 protein kinase as a target for the treatment of inflammatory disease. Current topics in medicinal chemistry. 2009;9(7):611–22. 19689369.
3. Duffield JS, Lupher M, Thannickal VJ, Wynn TA, Host responses in tissue repair and fibrosis. Annual review of pathology. 2013;8:241–76. doi: 10.1146/annurev-pathol-020712-16393023092186; PubMed Central PMCID: PMC3789589.
4. Wynn TA, Ramalingam TR, Mechanisms of fibrosis: therapeutic translation for fibrotic disease. Nat Med. 2012;18(7):1028–40. doi: 10.1038/nm.280722772564; PubMed Central PMCID: PMC3405917.
5. Wilson MS, Mentink-Kane MM, Pesce JT, Ramalingam TR, Thompson R, Wynn TA, Immunopathology of schistosomiasis. Immunol Cell Biol. 2007;85(2):148–54. Epub 2006/12/13. doi: 10.1038/sj.icb.710001417160074; PubMed Central PMCID: PMC3437548.
6. Schwartz C, Oeser K, Prazeres da Costa C, Layland LE, Voehringer D, T cell-derived IL-4/IL-13 protects mice against fatal Schistosoma mansoni infection independently of basophils. J Immunol. 2014;193(7):3590–9. Epub 2014/08/31. doi: 10.4049/jimmunol.140115525172500.
7. Herbert DR, Orekov T, Perkins C, Rothenberg ME, Finkelman FD, IL-4R alpha expression by bone marrow-derived cells is necessary and sufficient for host protection against acute schistosomiasis. J Immunol. 2008;180(7):4948–55. 18354220; PubMed Central PMCID: PMC2921971.
8. Herbert DR, Holscher C, Mohrs M, Arendse B, Schwegmann A, Radwanska M, et al. Alternative macrophage activation is essential for survival during schistosomiasis and downmodulates T helper 1 responses and immunopathology. Immunity. 2004;20(5):623–35. 15142530.
9. Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity. 2014;41(1):14–20. Epub 2014/07/19. doi: 10.1016/j.immuni.2014.06.00825035950; PubMed Central PMCID: PMC4123412.
10. Gause WC, Wynn TA, Allen JE, Type 2 immunity and wound healing: evolutionary refinement of adaptive immunity by helminths. Nat Rev Immunol. 2013;13(8):607–14. Epub 2013/07/06. doi: 10.1038/nri347623827958; PubMed Central PMCID: PMC3789590.
11. Wynn TA, IL-13 effector functions. Annu Rev Immunol. 2003;21:425–56. Epub 2003/03/05. doi: 10.1146/annurev.immunol.21.120601.14114212615888.
12. Barron L, Wynn TA, Macrophage activation governs schistosomiasis-induced inflammation and fibrosis. Eur J Immunol. 2011;41(9):2509–14. Epub 2011/09/29. doi: 10.1002/eji.20114186921952807; PubMed Central PMCID: PMC3408543.
13. Nair MG, Du Y, Perrigoue JG, Zaph C, Taylor JJ, Goldschmidt M, et al. Alternatively activated macrophage-derived RELM-{alpha} is a negative regulator of type 2 inflammation in the lung. J Exp Med. 2009;206(4):937–52. Epub 2009/04/08. doi: 10.1084/jem.2008204819349464; PubMed Central PMCID: PMC2715126.
14. Pesce JT, Ramalingam TR, Mentink-Kane MM, Wilson MS, El Kasmi KC, Smith AM, et al. Arginase-1-expressing macrophages suppress Th2 cytokine-driven inflammation and fibrosis. PLoS Pathog. 2009;5(4):e1000371. Epub 2009/04/11. doi: 10.1371/journal.ppat.100037119360123; PubMed Central PMCID: PMC2660425.
15. Pesce JT, Ramalingam TR, Wilson MS, Mentink-Kane MM, Thompson RW, Cheever AW, et al. Retnla (relmalpha/fizz1) suppresses helminth-induced Th2-type immunity. PLoS Pathog. 2009;5(4):e1000393. Epub 2009/04/22. doi: 10.1371/journal.ppat.100039319381262; PubMed Central PMCID: PMC2663845.
16. Gantke T, Sriskantharajah S, Ley SC, Regulation and function of TPL-2, an IkappaB kinase-regulated MAP kinase kinase kinase. Cell Res. 2011;21(1):131–45. Epub 2010/12/08. doi: 10.1038/cr.2010.17321135874; PubMed Central PMCID: PMC3193413.
17. McNab FW, Ewbank J, Rajsbaum R, Stavropoulos E, Martirosyan A, Redford PS, et al. TPL-2-ERK1/2 signaling promotes host resistance against intracellular bacterial infection by negative regulation of type I IFN production. J Immunol. 2013;191(4):1732–43. Epub 2013/07/12. doi: 10.4049/jimmunol.130014623842752; PubMed Central PMCID: PMC3796877.
18. Watford WT, Hissong BD, Durant LR, Yamane H, Muul LM, Kanno Y, et al. Tpl2 kinase regulates T cell interferon-gamma production and host resistance to Toxoplasma gondii. J Exp Med. 2008;205(12):2803–12. Epub 2008/11/13. doi: 10.1084/jem.2008146119001140; PubMed Central PMCID: PMC2585846.
19. Sriskantharajah S, Guckel E, Tsakiri N, Kierdorf K, Brender C, Ben-Addi A, et al. Regulation of experimental autoimmune encephalomyelitis by TPL-2 kinase. J Immunol. 2014;192(8):3518–29. doi: 10.4049/jimmunol.130017224639351; PubMed Central PMCID: PMC3979668.
20. Dumitru CD, Ceci JD, Tsatsanis C, Kontoyiannis D, Stamatakis K, Lin JH, et al. TNF-alpha induction by LPS is regulated posttranscriptionally via a Tpl2/ERK-dependent pathway. Cell. 2000;103(7):1071–83. Epub 2001/02/13. 11163183.
21. Rowley SM, Kuriakose T, Dockery LM, Tran-Ngyuen T, Gingerich AD, Wei L, et al. Tumor progression locus 2 (Tpl2) kinase promotes chemokine receptor expression and macrophage migration during acute inflammation. J Biol Chem. 2014;289(22):15788–97. Epub 2014/04/10. doi: 10.1074/jbc.M114.55934424713702; PubMed Central PMCID: PMC4140933.
22. Sanz-Garcia C, Nagy LE, Lasuncion MA, Fernandez M, Alemany S, Cot/tpl2 participates in the activation of macrophages by adiponectin. J Leukoc Biol. 2014;95(6):917–30. Epub 2014/02/18. doi: 10.1189/jlb.091348624532642; PubMed Central PMCID: PMC4021433.
23. Lopez-Pelaez M, Fumagalli S, Sanz C, Herrero C, Guerra S, Fernandez M, et al. Cot/tpl2-MKK1/2-Erk1/2 controls mTORC1-mediated mRNA translation in Toll-like receptor-activated macrophages. Mol Biol Cell. 2012;23(15):2982–92. Epub 2012/06/08. doi: 10.1091/mbc.E12-02-013522675026; PubMed Central PMCID: PMC3408424.
24. Bandow K, Kusuyama J, Shamoto M, Kakimoto K, Ohnishi T, Matsuguchi T, LPS-induced chemokine expression in both MyD88-dependent and -independent manners is regulated by Cot/Tpl2-ERK axis in macrophages. FEBS Lett. 2012;586(10):1540–6. Epub 2012/06/08. doi: 10.1016/j.febslet.2012.04.01822673523.
25. Lopez-Pelaez M, Soria-Castro I, Bosca L, Fernandez M, Alemany S, Cot/tpl2 activity is required for TLR-induced activation of the Akt p70 S6k pathway in macrophages: Implications for NO synthase 2 expression. Eur J Immunol. 2011;41(6):1733–41. Epub 2011/04/07. doi: 10.1002/eji.20104110121469113.
26. Mielke LA, Elkins KL, Wei L, Starr R, Tsichlis PN, O'Shea JJ, et al. Tumor progression locus 2 (Map3k8) is critical for host defense against Listeria monocytogenes and IL-1 beta production. J Immunol. 2009;183(12):7984–93. Epub 2009/11/26. doi: 10.4049/jimmunol.090133619933865; PubMed Central PMCID: PMC2946069.
27. Zhang M, Jin W, Zhou X, Yu J, Lee AJ, Sun SC, Deregulation of Tpl2 and NF-kappaB signaling and induction of macrophage apoptosis by the anti-depressant drug lithium. Cell Signal. 2009;21(4):559–66. Epub 2009/01/23. doi: 10.1016/j.cellsig.2008.12.01019159680; PubMed Central PMCID: PMC2688402.
28. Rousseau S, Papoutsopoulou M, Symons A, Cook D, Lucocq JM, Prescott AR, et al. TPL2-mediated activation of ERK1 and ERK2 regulates the processing of pre-TNF alpha in LPS-stimulated macrophages. J Cell Sci. 2008;121(Pt 2):149–54. Epub 2008/01/12. doi: 10.1242/jcs.01867118187448.
29. Cho J, Melnick M, Solidakis GP, Tsichlis PN, Tpl2 (tumor progression locus 2) phosphorylation at Thr290 is induced by lipopolysaccharide via an Ikappa-B Kinase-beta-dependent pathway and is required for Tpl2 activation by external signals. J Biol Chem. 2005;280(21):20442–8. Epub 2005/03/22. doi: 10.1074/jbc.M41355420015778223.
30. Wilson MS, Madala SK, Ramalingam TR, Gochuico BR, Rosas IO, Cheever AW, et al. Bleomycin and IL-1beta-mediated pulmonary fibrosis is IL-17A dependent. J Exp Med. 2010;207(3):535–52. doi: 10.1084/jem.2009212120176803; PubMed Central PMCID: PMC2839145.
31. Li LF, Liao SK, Huang CC, Hung MJ, Quinn DA, Serine/threonine kinase-protein kinase B and extracellular signal-regulated kinase regulate ventilator-induced pulmonary fibrosis after bleomycin-induced acute lung injury: a prospective, controlled animal experiment. Crit Care. 2008;12(4):R103. doi: 10.1186/cc698318691424; PubMed Central PMCID: PMCPMC2575592.
32. Perugorria MJ, Murphy LB, Fullard N, Chakraborty JB, Vyrla D, Wilson CL, et al. Tumor progression locus 2/Cot is required for activation of extracellular regulated kinase in liver injury and toll-like receptor-induced TIMP-1 gene transcription in hepatic stellate cells in mice. Hepatology. 2013;57(3):1238–49. Epub 2012/10/20. doi: 10.1002/hep.2610823080298.
33. Kaviratne M, Hesse M, Leusink M, Cheever AW, Davies SJ, McKerrow JH, et al. IL-13 activates a mechanism of tissue fibrosis that is completely TGF-beta independent. J Immunol. 2004;173(6):4020–9. 15356151.
34. Baumgart M, Tompkins F, Leng J, Hesse M, Naturally occurring CD4+Foxp3+ regulatory T cells are an essential, IL-10-independent part of the immunoregulatory network in Schistosoma mansoni egg-induced inflammation. J Immunol. 2006;176(9):5374–87. Epub 2006/04/20. 16622005.
35. Watford WT, Wang CC, Tsatsanis C, Mielke LA, Eliopoulos AG, Daskalakis C, et al. Ablation of tumor progression locus 2 promotes a type 2 Th cell response in Ovalbumin-immunized mice. J Immunol. 2010;184(1):105–13. Epub 2009/12/04. doi: 10.4049/jimmunol.080373019955521; PubMed Central PMCID: PMC3044327.
36. Serebrennikova OB, Tsatsanis C, Mao C, Gounaris E, Ren W, Siracusa LD, et al. Tpl2 ablation promotes intestinal inflammation and tumorigenesis in Apcmin mice by inhibiting IL-10 secretion and regulatory T-cell generation. Proc Natl Acad Sci U S A. 2012;109(18):E1082–91. Epub 2012/03/28. doi: 10.1073/pnas.111509810922451924; PubMed Central PMCID: PMC3344997.
37. Wu J, Green N, Hotchandani R, Hu Y, Condon J, Huang A, et al. Selective inhibitors of tumor progression loci-2 (Tpl2) kinase with potent inhibition of TNF-alpha production in human whole blood. Bioorg Med Chem Lett. 2009;19(13):3485–8. doi: 10.1016/j.bmcl.2009.05.00919464884.
38. Qi B, Newcomer RG, Sang QX, ADAM19/adamalysin 19 structure, function, and role as a putative target in tumors and inflammatory diseases. Curr Pharm Des. 2009;15(20):2336–48. Epub 2009/07/16. 19601835.
39. Makino H, Aono Y, Azuma M, Kishi M, Yokota Y, Kinoshita K, et al. Antifibrotic effects of CXCR4 antagonist in bleomycin-induced pulmonary fibrosis in mice. J Med Invest. 2013;60(1–2):127–37. Epub 2013/04/26. 23614921.
40. Nkyimbeng T, Ruppert C, Shiomi T, Dahal B, Lang G, Seeger W, et al. Pivotal role of matrix metalloproteinase 13 in extracellular matrix turnover in idiopathic pulmonary fibrosis. PLoS One. 2013;8(9):e73279. Epub 2013/09/12. doi: 10.1371/journal.pone.007327924023851; PubMed Central PMCID: PMC3759404.
41. Le LP, Garibyan L, Lara D, Finberg KE, Iafrate AJ, Duncan LM, et al. Fibrosis-associated single-nucleotide polymorphisms in TGFB1 and CAV1 are not associated with the development of nephrogenic systemic fibrosis. Am J Dermatopathol. 2013;35(3):351–6. Epub 2012/10/12. doi: 10.1097/DAD.0b013e31826c550823051628.
42. Henderson NC, Arnold TD, Katamura Y, Giacomini MM, Rodriguez JD, McCarty JH, et al. Targeting of alphav integrin identifies a core molecular pathway that regulates fibrosis in several organs. Nat Med. 2013;19(12):1617–24. Epub 2013/11/13. doi: 10.1038/nm.328224216753; PubMed Central PMCID: PMC3855865.
43. Todd NW, Luzina IG, Atamas SP, Molecular and cellular mechanisms of pulmonary fibrosis. Fibrogenesis Tissue Repair. 2012;5(1):11. Epub 2012/07/25. doi: 10.1186/1755-1536-5-1122824096; PubMed Central PMCID: PMC3443459.
44. Huang SC, Everts B, Ivanova Y, O'Sullivan D, Nascimento M, Smith AM, et al. Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages. Nat Immunol. 2014;15(9):846–55. Epub 2014/08/05. doi: 10.1038/ni.295625086775; PubMed Central PMCID: PMC4139419.
45. Jager J, Gremeaux T, Gonzalez T, Bonnafous S, Debard C, Laville M, et al. Tpl2 kinase is upregulated in adipose tissue in obesity and may mediate interleukin-1beta and tumor necrosis factor-{alpha} effects on extracellular signal-regulated kinase activation and lipolysis. Diabetes. 2010;59(1):61–70. Epub 2009/10/08. doi: 10.2337/db09-047019808894; PubMed Central PMCID: PMC2797946.
46. Bergan HE, Kittilson JD, Sheridan MA, PKC and ERK mediate GH-stimulated lipolysis. J Mol Endocrinol. 2013;51(2):213–24. Epub 2013/06/21. doi: 10.1530/JME-13-003923785126.
47. Moon HS, Lee HG, Seo JH, Guo DD, Kim IY, Chung CS, et al. Lipolysis is stimulated by PEGylated conjugated linoleic acid through the cyclic adenosine monophosphate-independent signaling pathway in 3T3-L1 cells: activation of MEK/ERK MAPK signaling pathway and hyper-secretion of adipo-cytokines. J Cell Physiol. 2008;214(2):283–94. Epub 2007/07/27. doi: 10.1002/jcp.2121917654485.
48. Ceppo F, Berthou F, Jager J, Dumas K, Cormont M, Tanti JF, Implication of the Tpl2 kinase in inflammatory changes and insulin resistance induced by the interaction between adipocytes and macrophages. Endocrinology. 2014;155(3):951–64. doi: 10.1210/en.2013-181524424060.
49. Chui PC, Guan HP, Lehrke M, Lazar MA, PPARgamma regulates adipocyte cholesterol metabolism via oxidized LDL receptor 1. J Clin Invest. 2005;115(8):2244–56. Epub 2005/07/12. doi: 10.1172/JCI2413016007265; PubMed Central PMCID: PMC1172230.
50. Diez JJ, Iglesias P, The role of the novel adipocyte-derived hormone adiponectin in human disease. Eur J Endocrinol. 2003;148(3):293–300. Epub 2003/03/04. 12611609.
51. Lovren F, Pan Y, Quan A, Szmitko PE, Singh KK, Shukla PC, et al. Adiponectin primes human monocytes into alternative anti-inflammatory M2 macrophages. Am J Physiol Heart Circ Physiol. 2010;299(3):H656–63. Epub 2010/07/14. doi: 10.1152/ajpheart.00115.201020622108; PubMed Central PMCID: PMC2944489.
52. Bonet ML, Ribot J, Palou A, Lipid metabolism in mammalian tissues and its control by retinoic acid. Biochim Biophys Acta. 2012;1821(1):177–89. Epub 2011/06/15. doi: 10.1016/j.bbalip.2011.06.00121669299.
53. Bobowski M, Vincent A, Steenackers A, Colomb F, Van Seuningen I, Julien S, et al. Estradiol represses the G(D3) synthase gene ST8SIA1 expression in human breast cancer cells by preventing NFkappaB binding to ST8SIA1 promoter. PLoS One. 2013;8(4):e62559. Epub 2013/04/30. doi: 10.1371/journal.pone.006255923626833; PubMed Central PMCID: PMC3633854.
54. Poynard T, Mathurin P, Lai CL, Guyader D, Poupon R, Tainturier MH, et al. A comparison of fibrosis progression in chronic liver diseases. Journal of hepatology. 2003;38(3):257–65. Epub 2003/02/15. 12586290.
55. Torok NJ, Dranoff JA, Schuppan D, Friedman SL, Strategies and endpoints of antifibrotic drug trials: Summary and recommendations from the AASLD Emerging Trends Conference, Chicago, June 2014. Hepatology. 2015;62(2):627–34. Epub 2015/01/30. doi: 10.1002/hep.2772025626988; PubMed Central PMCID: PMC4515973.
56. Wynn TA, Cheever AW, Jankovic D, Poindexter RW, Caspar P, Lewis FA, et al. An IL-12-based vaccination method for preventing fibrosis induced by schistosome infection. Nature. 1995;376(6541):594–6. doi: 10.1038/376594a07637808.
57. Liu Y, She W, Wang F, Li J, Wang J, Jiang W, 3, 3'-Diindolylmethane alleviates steatosis and the progression of NASH partly through shifting the imbalance of Treg/Th17 cells to Treg dominance. International immunopharmacology. 2014;23(2):489–98. doi: 10.1016/j.intimp.2014.09.02425281898.
58. Meng F, Wang K, Aoyama T, Grivennikov SI, Paik Y, Scholten D, et al. Interleukin-17 signaling in inflammatory, Kupffer cells, and hepatic stellate cells exacerbates liver fibrosis in mice. Gastroenterology. 2012;143(3):765–76.e1–3. doi: 10.1053/j.gastro.2012.05.04922687286; PubMed Central PMCID: PMC3635475.
59. Hesse M, Modolell M, La Flamme AC, Schito M, Fuentes JM, Cheever AW, et al. Differential regulation of nitric oxide synthase-2 and arginase-1 by type 1/type 2 cytokines in vivo: granulomatous pathology is shaped by the pattern of L-arginine metabolism. J Immunol. 2001;167(11):6533–44. Epub 2001/11/21. 11714822.
60. Koliaraki V, Roulis M, Kollias G, Tpl2 regulates intestinal myofibroblast HGF release to suppress colitis-associated tumorigenesis. J Clin Invest. 2012;122(11):4231–42. doi: 10.1172/JCI6391723064365; PubMed Central PMCID: PMC3484449.
61. Vannella KM, Barron L, Borthwick LA, Kindrachuk KN, Narasimhan PB, Hart KM, et al. Incomplete deletion of IL-4Ralpha by LysM(Cre) reveals distinct subsets of M2 macrophages controlling inflammation and fibrosis in chronic schistosomiasis. PLoS Pathog. 2014;10(9):e1004372. Epub 2014/09/12. doi: 10.1371/journal.ppat.100437225211233; PubMed Central PMCID: PMC4161449.
62. Hume DA, Applications of myeloid-specific promoters in transgenic mice support in vivo imaging and functional genomics but do not support the concept of distinct macrophage and dendritic cell lineages or roles in immunity. J Leukoc Biol. 2011;89(4):525–38. Epub 2010/12/21. doi: 10.1189/jlb.081047221169519.
63. Barnden MJ, Allison J, Heath WR, Carbone FR, Defective TCR expression in transgenic mice constructed using cDNA-based alpha- and beta-chain genes under the control of heterologous regulatory elements. Immunol Cell Biol. 1998;76(1):34–40. doi: 10.1046/j.1440-1711.1998.00709.x9553774.
64. Mohrs K, Wakil AE, Killeen N, Locksley RM, Mohrs M, A two-step process for cytokine production revealed by IL-4 dual-reporter mice. Immunity. 2005;23(4):419–29. doi: 10.1016/j.immuni.2005.09.00616226507; PubMed Central PMCID: PMCPMC2826320.
65. Wan YY, Flavell RA, Identifying Foxp3-expressing suppressor T cells with a bicistronic reporter. Proc Natl Acad Sci U S A. 2005;102(14):5126–31. doi: 10.1073/pnas.050170110215795373; PubMed Central PMCID: PMCPMC556008.
66. Lee PP, Fitzpatrick DR, Beard C, Jessup HK, Lehar S, Makar KW, et al. A critical role for Dnmt1 and DNA methylation in T cell development, function, and survival. Immunity. 2001;15(5):763–74. 11728338.
67. Clausen BE, Burkhardt C, Reith W, Renkawitz R, Forster I, Conditional gene targeting in macrophages and granulocytes using LysMcre mice. Transgenic Res. 1999;8(4):265–77. 10621974.
68. Erben U, Loddenkemper C, Doerfel K, Spieckermann S, Haller D, Heimesaat MM, et al. A guide to histomorphological evaluation of intestinal inflammation in mouse models. Int J Clin Exp Pathol. 2014;7(8):4557–76. 25197329; PubMed Central PMCID: PMCPMC4152019.
69. Dalton JP, Day SR, Drew AC, Brindley PJ, A method for the isolation of schistosome eggs and miracidia free of contaminating host tissues. Parasitology. 1997;115 (Pt 1):29–32. 9226954.
70. Pesek JJ, Matyska MT, Fischer SM, Sana TR, Analysis of hydrophilic metabolites by high-performance liquid chromatography-mass spectrometry using a silica hydride-based stationary phase. Journal of chromatography A. 2008;1204(1):48–55. Epub 2008/08/15. doi: 10.1016/j.chroma.2008.07.07718701108.
71. Larrouy-Maumus G, Biswas T, Hunt DM, Kelly G, Tsodikov OV, de Carvalho LP, Discovery of a glycerol 3-phosphate phosphatase reveals glycerophospholipid polar head recycling in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A. 2013;110(28):11320–5. Epub 2013/06/27. doi: 10.1073/pnas.122159711023801751; PubMed Central PMCID: PMC3710836.