Cytokines have been implicated in a variety of physiological processes involving lymphoid tissue development, lymphocyte activation, and control of regenerative processes such as wound healing. The first characterization of a cytokine implicated in abolishing or killing tumor cells – the tumor necrosis factor (TNF) – fostered and boosted a completely new field of research that in addition to cancer research started to generate an overwhelming amount of knowledge in immunology, various pathological processes, and other fields of research. Due to the complex networks and versatile functions of cytokines, it soon became clear that cytokines can possess diametric functions in various biological processes. As for tumor research it was shown that some cytokines – depending on the type of organ, the time of action, gender, and the cellular environment – can have either pro- or anticarcinogenic action. For those cytokines reported to be procarcinogenic, this could be accomplished by directly acting as oncogenes or generating an inflammatory environment that is procarcinogenic. Here we review a novel role for TNF family members – in particular lymphotoxin (LT) α and β – in physiology and in driving tumorigenesis, with special focus on the liver. We believe that recent findings on this particular cytokine might have strong implications for the therapy of liver cancer or other inflammation-induced cancer types.

1.
Medzhitov R: Inflammation 2010: new adventures of an old flame. Cell 2010;140:771–776.
2.
Pecchi E, Dallaporta M, Jean A, Thirion S, Troadec JD: Prostaglandins and sickness behavior: old story, new insights. Physiol Behav 2009;97:279–292.
3.
Tracey KJ: The inflammatory reflex. Nature 2002;420:853–859.
4.
Feghali CA, Wright TM: Cytokines in acute and chronic inflammation. Front Biosci 1997;2:d12–d26.
5.
Colotta F, Allavena P, Sica A, Garlanda C, Mantovani A: Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 2009;30:1073–1081.
6.
Hanahan D, Weinberg RA: Hallmarks of cancer: the next generation. Cell 2011;144:646–674.
7.
Grivennikov SI, Greten FR, Karin M: Immunity, inflammation, and cancer. Cell 2010;140:883–899.
8.
Takahashi H, Ogata H, Nishigaki R, Broide DH, Karin M: Tobacco smoke promotes lung tumorigenesis by triggering IKKbeta- and JNK1-dependent inflammation. Cancer Cell 2010;17:89–97.
9.
Park EJ, Lee JH, Yu GY, et al: Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell 2010;140:197–208.
10.
Calle EE: Obesity and cancer. BMJ 2007;335:1107–1108.
11.
Bollrath J, Greten FR: IKK/NF-kappaB and STAT3 pathways: central signalling hubs in inflammation-mediated tumour promotion and metastasis. EMBO Rep 2009;10:1314–1319.
12.
Zong WX, Thompson CB: Necrotic death as a cell fate. Genes Dev 2006;20:1–15.
13.
Rodier F, Coppe JP, Patil CK, et al: Persistent DNA damage signalling triggers senescence-associated inflammatory cytokine secretion. Nat Cell Biol 2009;11:973–979.
14.
Ammirante M, Luo JL, Grivennikov S, Nedospasov S, Karin M: B-cell-derived lymphotoxin promotes castration-resistant prostate cancer. Nature 2010;464:302–305.
15.
Sayi A, Kohler E, Hitzler I, et al: The CD4+ T cell-mediated IFN-gamma response to Helicobacter infection is essential for clearance and determines gastric cancer risk. J Immunol 2009;182:7085–101.
16.
Murdoch C, Muthana M, Coffelt SB, Lewis CE: The role of myeloid cells in the promotion of tumour angiogenesis. Nature Rev Cancer 2008;8:618–631.
17.
Condeelis J, Pollard JW: Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 2006;124:263–266.
18.
Lin WW, Karin M: A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest 2007;117:1175–1183.
19.
Chung JY, Park YC, Ye H, Wu H: All TRAFs are not created equal: common and distinct molecular mechanisms of TRAF-mediated signal transduction. J Cell Sci 2002;115:679–688.
20.
Dempsey PW, Doyle SE, He JQ, Cheng G: The signaling adaptors and pathways activated by TNF superfamily. Cytokine Growth Factor Rev 2003;14:193–209.
21.
Chinnaiyan AM, Tepper CG, Seldin MF, et al: FADD/MORT1 is a common mediator of CD95 (Fas/APO-1) and tumor necrosis factor receptor-induced apoptosis. J Biol Chem 1996;271:4961–4965.
22.
Kischkel FC, Lawrence DA, Chuntharapai A, Schow P, Kim KJ, Ashkenazi A: Apo2L/TRAIL-dependent recruitment of endogenous FADD and caspase-8 to death receptors 4 and 5. Immunity 2000;12:611–620.
23.
Micheau O, Tschopp J: Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 2003;114:181–190.
24.
Hehlgans T, Pfeffer K: The intriguing biology of the tumour necrosis factor/tumour necrosis factor receptor superfamily: players, rules and the games. Immunology 2005;115:1–20.
25.
Eck MJ, Sprang SR: The structure of tumor necrosis factor-alpha at 2.6 A resolution: implications for receptor binding. J Biol Chem 1989;264:17595–17605.
26.
Loetscher H, Stueber D, Banner D, Mackay F, Lesslauer W: Human tumor necrosis factor alpha (TNF alpha) mutants with exclusive specificity for the 55-kDa or 75-kDa TNF receptors. J Biol Chem 1993;268:26350–26357.
27.
Bossen C, Cachero TG, Tardivel A, et al: TACI, unlike BAFF-R, is solely activated by oligomeric BAFF and APRIL to support survival of activated B cells and plasmablasts. Blood 2008;111:1004–1012.
28.
Browning JL, Ngam-ek A, Lawton P, et al: Lymphotoxin beta, a novel member of the TNF family that forms a heteromeric complex with lymphotoxin on the cell surface. Cell 1993;72:847–856.
29.
Browning JL, Dougas I, Ngam-ek A, et al: Characterization of surface lymphotoxin forms: use of specific monoclonal antibodies and soluble receptors. J Immunol 1995;154:33–46.
30.
Young J, Yu X, Wolslegel K, et al: Lymphotoxin-alphabeta heterotrimers are cleaved by metalloproteinases and contribute to synovitis in rheumatoid arthritis. Cytokine 2010;51:78–86.
31.
Ware CF: Network communications: lymphotoxins, LIGHT, and TNF. Annu Rev Immunol 2005;23:787–819.
32.
Vandenabeele P, Galluzzi L, Vanden Berghe T, Kroemer G: Molecular mechanisms of necroptosis: an ordered cellular explosion. Nat Rev Mol Cell Biol 2010;11:700–714.
33.
Remouchamps C, Boutaffala L, Ganeff C, Dejardin E: Biology and signal transduction pathways of the lymphotoxin-alphabeta/ LTbetaR system. Cytokine Growth Factor Rev 2011;22:301–310.
34.
Ganeff C, Remouchamps C, Boutaffala L, et al: Induction of the alternative NF-kappaB pathway by lymphotoxin alphabeta (LTalphabeta) relies on internalization of LTbeta receptor. Mol Cell Biol 2011;31:4319–4334.
35.
Coope HJ, Atkinson PG, Huhse B, et al: CD40 regulates the processing of NF-kappaB2 p100 to p52. EMBO J 2002;21:5375–5385.
36.
Pomerantz JL, Baltimore D: Two pathways to NF-kappaB. Mol Cell 2002;10:693–695.
37.
Dejardin E, Droin NM, Delhase M, et al: The lymphotoxin-beta receptor induces different patterns of gene expression via two NF-kappaB pathways. Immunity 2002;17:525–535.
38.
Senftleben U, Cao Y, Xiao G, et al: Activation by IKKalpha of a second, evolutionary conserved, NF-kappa B signaling pathway. Science 2001;293:1495–1499.
39.
Ling L, Cao Z, Goeddel DV: NF-kappaB-inducing kinase activates IKK-alpha by phosphorylation of Ser-176. Proc Natl Acad Sci USA 1998;95:3792–3797.
40.
Weih F, Caamano J: Regulation of secondary lymphoid organ development by the nuclear factor-kappaB signal transduction pathway. Immunol Rev 2003;195:91–105.
41.
Zhu M, Fu YX: The role of core TNF/LIGHT family members in lymph node homeostasis and remodeling. Immunol Rev 2011;244:75–84.
42.
Aggarwal BB: Signalling pathways of the TNF superfamily: a double-edged sword. Nat Rev Immunology 2003;3:745–756.
43.
Norris PS, Ware CF: The LT beta R signaling pathway: advances in experimental medicine and biology 2007;597:160–172.
44.
De Togni P, Goellner J, Ruddle NH, et al: Abnormal development of peripheral lymphoid organs in mice deficient in lymphotoxin. Science 1994;264:703–707.
45.
Banks TA, Rouse BT, Kerley MK, et al: Lymphotoxin-alpha-deficient mice: effects on secondary lymphoid organ development and humoral immune responsiveness. J Immunol 1995;155:1685–1693.
46.
Alimzhanov MB, Kuprash DV, Kosco-Vilbois MH, et al: Abnormal development of secondary lymphoid tissues in lymphotoxin beta-deficient mice. Proc Natl Acad Sci USA 1997;94:9302–9307.
47.
Koni PA, Sacca R, Lawton P, Browning JL, Ruddle NH, Flavell RA: Distinct roles in lymphoid organogenesis for lymphotoxins alpha and beta revealed in lymphotoxin beta-deficient mice. Immunity 1997;6:491–500.
48.
Ngo VN, Korner H, Gunn MD, et al: Lymphotoxin alpha/beta and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleen. J Exp Med 1999;189:403–412.
49.
Futterer A, Mink K, Luz A, Kosco-Vilbois MH, Pfeffer K: The lymphotoxin beta receptor controls organogenesis and affinity maturation in peripheral lymphoid tissues. Immunity 1998;9:59–70.
50.
Rennert PD, Browning JL, Mebius R, Mackay F, Hochman PS: Surface lymphotoxin alpha/beta complex is required for the development of peripheral lymphoid organs. J Exp Med 1996;184:1999–2006.
51.
Shinkura R, Kitada K, Matsuda F, et al: Alymphoplasia is caused by a point mutation in the mouse gene encoding Nf-kappa b-inducing kinase. Nat Genet 1999;22:74–77.
52.
Veiga-Fernandes H, Coles MC, Foster KE, et al: Tyrosine kinase receptor RET is a key regulator of Peyer’s patch organogenesis. Nature 2007;446:547–551.
53.
Adachi S, Yoshida H, Kataoka H, Nishikawa S: Three distinctive steps in Peyer’s patch formation of murine embryo. Int Immunol 1997;9:507–514.
54.
Hashi H, Yoshida H, Honda K, et al: Compartmentalization of Peyer’s patch anlagen before lymphocyte entry. J Immunol 2001;166:3702–3709.
55.
Honda K, Nakano H, Yoshida H, et al: Molecular basis for hematopoietic/mesenchymal interaction during initiation of Peyer’s patch organogenesis. J Exp Med 2001;193:621–630.
56.
Ansel KM, Ngo VN, Hyman PL, et al: A chemokine-driven positive feedback loop organizes lymphoid follicles. Nature 2000;406:309–314.
57.
Ambrose CT: Immunology’s first priority dispute – an account of the 17th-century Rudbeck-Bartholin feud. Cell Immunol 2006;242:1–8.
58.
Kim D, Mebius RE, MacMicking JD, et al: Regulation of peripheral lymph node genesis by the tumor necrosis factor family member TRANCE. J Exp Med 2000;192:1467–1478.
59.
Rennert PD, James D, Mackay F, Browning JL, Hochman PS: Lymph node genesis is induced by signaling through the lymphotoxin beta receptor. Immunity 1998;9:71–79.
60.
Hamada H, Hiroi T, Nishiyama Y, et al: Identification of multiple isolated lymphoid follicles on the antimesenteric wall of the mouse small intestine. J Immunol 2002;168:57–64.
61.
Lorenz RG, Chaplin DD, McDonald KG, McDonough JS, Newberry RD: Isolated lymphoid follicle formation is inducible and dependent upon lymphotoxin-sufficient B lymphocytes, lymphotoxin beta receptor, and TNF receptor I function. J Immunol 2003;170:5475–5482.
62.
Bouskra D, Brezillon C, Berard M, et al: Lymphoid tissue genesis induced by commensals through NOD1 regulates intestinal homeostasis. Nature 2008;456:507–510.
63.
Eberl G, Littman DR: Thymic origin of intestinal alphabeta T cells revealed by fate mapping of RORgammat+ cells. Science 2004;305:248–251.
64.
Spahn TW, Maaser C, Eckmann L, et al: The lymphotoxin-beta receptor is critical for control of murine Citrobacter rodentium- induced colitis. Gastroenterology 2004;127:1463–1473.
65.
Lee YK, Mazmanian SK: Has the microbiota played a critical role in the evolution of the adaptive immune system? Science 2010;330:1768–1773.
66.
Brandtzaeg P, Farstad IN, Johansen FE, Morton HC, Norderhaug IN, Yamanaka T: The B-cell system of human mucosae and exocrine glands. Immunol Rev 1999;171:45–87.
67.
Fagarasan S: Intestinal IgA synthesis: a primitive form of adaptive immunity that regulates microbial communities in the gut. Curr Top Microbiol Immunol 2006;308:137–153.
68.
Macpherson AJ, Smith K: Mesenteric lymph nodes at the center of immune anatomy. J Exp Med 2006;203:497–500.
69.
McWilliams M, Phillips-Quagliata JM, Lamm ME: Mesenteric lymph node B lymphoblasts which home to the small intestine are precommitted to IgA synthesis. J Exp Med 1977;145:866–875.
70.
Yamamoto M, Rennert P, McGhee JR, et al: Alternate mucosal immune system: organized Peyer’s patches are not required for IgA responses in the gastrointestinal tract. J Immunol 2000;164:5184–5191.
71.
Spahn TW, Fontana A, Faria AM, et al: Induction of oral tolerance to cellular immune responses in the absence of Peyer’s patches. Eur J Immunol 2001;31:1278–1287.
72.
Ryffel B, Le Hir M, Muller M, Eugster HP: Correction of the TNF-LT alpha-deficient phenotype by bone marrow transplantation. Dev Immunol 1998;6:253–260.
73.
Kang HS, Chin RK, Wang Y, et al: Signaling via LTbetaR on the lamina propria stromal cells of the gut is required for IgA production. Nat Immunol 2002;3:576–582.
74.
Agyekum S, Church A, Sohail M, et al: Expression of lymphotoxin-beta (LT-beta) in chronic inflammatory conditions. J Pathol 2003;199:115–121.
75.
Jungbeck M, Daller B, Federhofer J, et al: Neutralization of LIGHT ameliorates acute dextran sodium sulphate-induced intestinal inflammation. Immunology 2009;128:451–458.
76.
Zheng Y, Valdez PA, Danilenko DM, et al: Interleukin-22 mediates early host defense against attaching and effacing bacterial pathogens. Nat Med 2008;14:282–289.
77.
Tumanov AV, Koroleva EP, Guo X, et al: Lymphotoxin controls the IL-22 protection pathway in gut innate lymphoid cells during mucosal pathogen challenge. Cell Host Microbe 2011;10:44–53.
78.
Barthel M, Hapfelmeier S, Quintanilla-Martinez L, et al: Pretreatment of mice with streptomycin provides a Salmonella enterica serovar Typhimurium colitis model that allows analysis of both pathogen and host. Infect Immun 2003;71:2839–2858.
79.
Messer G, Spengler U, Jung MC, et al: Polymorphic structure of the tumor necrosis factor (TNF) locus: an NcoI polymorphism in the first intron of the human TNF-beta gene correlates with a variant amino acid in position 26 and a reduced level of TNF-beta production. J Exp Med 1991;173:209–219.
80.
Chae YS, Kim JG, Sohn SK, et al: Lymphotoxin alfa and receptor-interacting protein kinase 1 gene polymorphisms may correlate with prognosis in patients with diffuse large B cell lymphoma treated with R-CHOP. Cancer Chemother Pharmacol 2010;65:571–577.
81.
Nonomura N, Tokizane T, Nakayama M, et al: Possible correlation between polymorphism in the tumor necrosis factor-beta gene and the clinicopathological features of bladder cancer in Japanese patients. Int J Urol 2006;13:971–976.
82.
Niwa Y, Ito H, Matsuo K, et al: Lymphotoxin-alpha polymorphisms and the risk of endometrial cancer in Japanese subjects. Gynecol Oncol 2007;104:586–590.
83.
Takei K, Ikeda S, Arai T, Tanaka N, Muramatsu M, Sawabe M: Lymphotoxin-alpha polymorphisms and presence of cancer in 1,536 consecutive autopsy cases. BMC Cancer 2008;8:235.
84.
Or YY, Chung GT, To KF, et al: Identification of a novel 12p13.3 amplicon in nasopharyngeal carcinoma. J Pathol 2010;220:97–107.
85.
Compagno M, Lim WK, Grunn A, et al: Mutations of multiple genes cause deregulation of NF-kappaB in diffuse large B-cell lymphoma. Nature 2009;459:717–721.
86.
Keats JJ, Fonseca R, Chesi M, et al: Promiscuous mutations activate the noncanonical NF-kappaB pathway in multiple myeloma. Cancer Cell 2007;12:131–144.
87.
Yamagishi M, Nakano K, Miyake A, et al: Polycomb-mediated loss of miR-31 activates NIK-dependent NF-kappaB pathway in adult T cell leukemia and other cancers. Cancer Cell 2012;21:121–135.
88.
Fujiwara S, Yamashita Y, Choi YL, et al: Transforming activity of the lymphotoxin-beta receptor revealed by expression screening. Biochem Biophys Res Commun 2005;338:1256–1262.
89.
Luo JL, Tan W, Ricono JM, et al: Nuclear cytokine-activated IKKalpha controls prostate cancer metastasis by repressing Maspin. Nature 2007;446:690–694.
90.
Tan W, Zhang W, Strasner A, et al: Tumour-infiltrating regulatory T cells stimulate mammary cancer metastasis through RANKL-RANK signalling. Nature 2011;470:548–553.
91.
Browning JL, Miatkowski K, Sizing I, et al: Signaling through the lymphotoxin beta receptor induces the death of some adenocarcinoma tumor lines. J Exp Med 1996;183:867–878.
92.
Lukashev M, LePage D, Wilson C, et al: Targeting the lymphotoxin-beta receptor with agonist antibodies as a potential cancer therapy. Cancer Res 2006;66:9617–9624.
93.
Rayet B, Gelinas C: Aberrant rel/nfkb genes and activity in human cancer. Oncogene 1999;18:6938–6947.
94.
Wang Y, Cui H, Schroering A, et al: NF-kappa B2 p100 is a pro-apoptotic protein with anti-oncogenic function. Nat Cell Biol 2002;4:888–893.
95.
Ito D, Back TC, Shakhov AN, Wiltrout RH, Nedospasov SA: Mice with a targeted mutation in lymphotoxin-alpha exhibit enhanced tumor growth and metastasis: impaired NK cell development and recruitment. J Immunol 1999;163:2809–2815.
96.
Zhou P, Fang X, McNally BA, et al: Targeting lymphotoxin-mediated negative selection to prevent prostate cancer in mice with genetic predisposition. Proc Natl Acad Sci USA 2009;106:17134–17139.
97.
Kim DH, Kim EM, Lee EH, et al: Human papillomavirus 16E6 suppresses major histocompatibility complex class I by upregulating lymphotoxin expression in human cervical cancer cells. Biochem Biophys Res Commun 2011;409:792–798.
98.
Rehm A, Mensen A, Schradi K, et al: Cooperative function of CCR7 and lymphotoxin in the formation of a lymphoma-permissive niche within murine secondary lymphoid organs. Blood 2011;118:1020–1033.
99.
Hehlgans T, Stoelcker B, Stopfer P, et al: Lymphotoxin-beta receptor immune interaction promotes tumor growth by inducing angiogenesis. Cancer Res 2002;62:4034–4040.
100.
Daller B, Musch W, Rohrl J, et al: Lymphotoxin-beta receptor activation by lymphotoxin-alpha(1)beta(2) and LIGHT promotes tumor growth in an NFkappaB-dependent manner. Int J Cancer 2011;128:1363–1370.
101.
Kuprash DV, Qin Z, Ito D, et al: Ablation of TNF or lymphotoxin signaling and the frequency of spontaneous tumors in p53-deficient mice. Cancer Lett 2008;268:70–75.
102.
Anders RA, Subudhi SK, Wang J, Pfeffer K, Fu YX: Contribution of the lymphotoxin beta receptor to liver regeneration. J Immunol 2005;175:1295–1300.
103.
Tumanov AV, Koroleva EP, Christiansen PA, et al: T cell-derived lymphotoxin regulates liver regeneration. Gastroenterology 2009;136:694–704 e4.
104.
Ruddell RG, Knight B, Tirnitz-Parker JE, et al: Lymphotoxin-beta receptor signaling regulates hepatic stellate cell function and wound healing in a murine model of chronic liver injury. Hepatology 2009;49:227–239.
105.
Lo JC, Wang Y, Tumanov AV, et al: Lymphotoxin beta receptor-dependent control of lipid homeostasis. Science 2007;316:285–288.
106.
Anand S, Wang P, Yoshimura K, et al: Essential role of TNF family molecule LIGHT as a cytokine in the pathogenesis of hepatitis. J Clin Invest 2006;116:1045–1051.
107.
An MM, Fan KX, Cao YB, et al: Lymphtoxin beta receptor-Ig protects from T-cell-mediated liver injury in mice through blocking LIGHT/HVEM signaling. Biol Pharm Bull 2006;29:2025–2030.
108.
Chen CM, You LR, Hwang LH, Lee YH: Direct interaction of hepatitis C virus core protein with the cellular lymphotoxin-beta receptor modulates the signal pathway of the lymphotoxin-beta receptor. J Virol 1997;71:9417–9426.
109.
Matsumoto M, Hsieh TY, Zhu N, et al: Hepatitis C virus core protein interacts with the cytoplasmic tail of lymphotoxin-beta receptor. J Virol 1997;71:1301–1309.
110.
Lowes KN, Croager EJ, Abraham LJ, Olynyk JK, Yeoh GC: Upregulation of lymphotoxin beta expression in liver progenitor (oval) cells in chronic hepatitis C. Gut 2003;52:1327–1332.
111.
Ng TI, Mo H, Pilot-Matias T, et al: Identification of host genes involved in hepatitis C virus replication by small interfering RNA technology. Hepatology 2007;45:1413–1421.
112.
Lee SH, Park SG, Lim SO, Jung G: The hepatitis B virus X protein up-regulates lymphotoxin alpha expression in hepatocytes. Biochim Biophys Acta 2005;1741:75–84.
113.
Washburn ML, Kovalev GI, Koroleva E, Fu YX, Su L: LIGHT induces distinct signals to clear an AAV-expressed persistent antigen in the mouse liver and to induce liver inflammation. PLoS One;5:e10585.
114.
Haybaeck J, Zeller N, Wolf MJ, et al: A lymphotoxin-driven pathway to hepatocellular carcinoma. Cancer Cell 2009;16:295–308.
115.
Wang Y, Koroleva EP, Kruglov AA, et al: Lymphotoxin beta receptor signaling in intestinal epithelial cells orchestrates innate immune responses against mucosal bacterial infection. Immunity 2010;32:403–413.
116.
Ehlers S, Holscher C, Scheu S, et al: The lymphotoxin beta receptor is critically involved in controlling infections with the intracellular pathogens Mycobacterium tuberculosis and Listeria monocytogenes. J Immunol 2003;170:5210–5218.
117.
Xu G, Liu D, Fan Y, et al: Lymphotoxin alpha beta 2 (membrane lymphotoxin) is critically important for resistance to Leishmania major infection in mice. J Immunol 2007;179:5358–5366.
118.
Engwerda CR, Ato M, Stager S, Alexander CE, Stanley AC, Kaye PM: Distinct roles for lymphotoxin-alpha and tumor necrosis factor in the control of Leishmania donovani infection. Am J Pathol 2004;165:2123–2133.
119.
Chiang EY, Kolumam GA, Yu X, et al: Targeted depletion of lymphotoxin-alpha-expressing TH1 and TH17 cells inhibits autoimmune disease. Nat Med 2009;15:766–773.
120.
Levisetti MG, Suri A, Frederick K, Unanue ER: Absence of lymph nodes in NOD mice treated with lymphotoxin-beta receptor immunoglobulin protects from diabetes. Diabetes 2004;53:3115–3119.
121.
Dharmana E, Keuter M, Netea MG, Verschueren IC, Kullberg BJ: Divergent effects of tumor necrosis factor-alpha and lymphotoxin-alpha on lethal endotoxemia and infection with live Salmonella typhimurium in mice. Eur Cytokine Netw 2002;13:104–109.
122.
Jungbeck M, Stopfer P, Bataille F, Nedospasov SA, Mannel DN, Hehlgans T: Blocking lymphotoxin beta receptor signalling exacerbates acute DSS-induced intestinal inflammation – opposite functions for surface lymphotoxin expressed by T and B lymphocytes. Mol Immunol 2008;45:34–41.
123.
Engwerda CR, Mynott TL, Sawhney S, De Souza JB, Bickle QD, Kaye PM: Locally up-regulated lymphotoxin alpha, not systemic tumor necrosis factor alpha, is the principle mediator of murine cerebral malaria. J Exp Med 2002;195:1371–1377.
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