title: Linking the microbiota and metabolic disease with lymphotoxin.
abstract: The field of lymphotoxin biology has seen many advances in the past decade. Notably, a role for lymphotoxin as a key effector cytokine has emerged to add to its foundational contribution to lymphoid organogenesis. It is now clear that lymphotoxin contributes to host defense for a wide variety of pathogens, and the lymphotoxin receptor is a defining feature of and regulatory mechanism in both innate and adaptive immunities. Specifically, lymphotoxin contributes to Th education, licensing of IL-22 production from type 3 innate lymphoid cells, and even maintains innate myeloid populations within the fully developed lymph node. Most recently, lymphotoxin has been implicated in regulation of the microbiota and metabolic disease. Early studies revealed that lymphotoxin might influence composition of the commensal microbiota through its regulation of immunological compartmentalization in the gut. Additionally, several epidemiological studies have linked polymorphisms in lymphotoxin to metabolic disease. Studies exploring the role of lymphotoxin in metabolic disease have demonstrated that lymphotoxin may influence metabolism both directly in the liver and indirectly through regulation of gut immune responses. It now appears that lymphotoxin may bridge the gap between altered composition of the commensal microbiota and metabolism.
authors: Committee on Immunology, University of Chicago, Chicago, IL 60637, USA. vupadhyay@uchicago.edu
authors: Vaibhav
authors: V
authors: Upadhyay
authors: Yang-Xin
authors: YX
authors: Fu
mesh_terms: D000818:Animals; D041981:Gastrointestinal Tract / Q000276:immunology / Q000382:microbiology*; D006801:Humans; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008659:Metabolic Diseases / Q000276:immunology*; D051379:Mice; D064307:Microbiota
chemical_list: D008233:Lymphotoxin-alpha
keywords: SFB; diabetes; lymphotoxin; metabolism; microbiota; obesity
references: Int J Cancer. 1985 Jul 15;36(1):69-73
references: 3874835
references: Science. 2011 Oct 14;334(6053):255-8
references: 21998396
references: Nature. 2012 Jul 5;487(7405):104-8
references: 22722865
references: Nat Genet. 2002 Dec;32(4):650-4
references: 12426569
references: Immunity. 2010 Mar 26;32(3):403-13
references: 20226692
references: Science. 2000 Jun 23;288(5474):2222-6
references: 10864873
references: Nature. 2013 Feb 7;494(7435):116-20
references: 23334413
references: Nat Immunol. 2012 May 27;13(7):681-90
references: 22634865
references: Nat Biotechnol. 2012 Jun 07;30(6):513-20
references: 22678395
references: Cell Host Microbe. 2011 Jul 21;10(1):44-53
references: 21767811
references: Immunity. 1998 Jul;9(1):59-70
references: 9697836
references: Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):2046-51
references: 21245292
references: J Exp Med. 2009 Jan 16;206(1):233-48
references: 19139167
references: Science. 2007 Apr 13;316(5822):285-8
references: 17431181
references: J Immunol. 2005 Jun 1;174(11):7217-25
references: 15905567
references: Nature. 2012 Feb 01;482(7384):179-85
references: 22297845
references: Immunity. 2012 Mar 23;36(3):415-26
references: 22386268
references: Science. 2010 Apr 9;328(5975):228-31
references: 20203013
references: J Mol Med (Berl). 2010 May;88(5):515-22
references: 20177654
references: Nature. 2007 Nov 1;450(7166):110-4
references: 17934446
references: Nature. 2006 Dec 21;444(7122):1027-31
references: 17183312
references: Science. 1994 Apr 29;264(5159):703-7
references: 8171322
references: Gastroenterology. 2012 Oct;143(4):913-6.e7
references: 22728514
references: J Exp Med. 2003 Dec 1;198(11):1643-52
references: 14638845
references: Nature. 2008 Nov 27;456(7221):507-10
references: 18987631
references: J Immunol. 2003 May 15;170(10):5210-8
references: 12734369
references: J Mol Med (Berl). 2004 Jul;82(7):477-83
references: 15175864
references: Proc Natl Acad Sci U S A. 2010 Apr 20;107(16):7419-24
references: 20360558
references: Gastroenterology. 2009 Nov;137(5):1716-24.e1-2
references: 19706296
references: Annu Rev Immunol. 1999;17:399-433
references: 10358764
references: Nat Rev Immunol. 2003 Apr;3(4):292-303
references: 12669020
references: Gastroenterology. 2004 Nov;127(5):1463-73
references: 15521015
references: Curr Opin Immunol. 1992 Jun;4(3):327-32
references: 1329840
references: Nature. 2009 Jan 22;457(7228):480-4
references: 19043404
references: Diabetologia. 2005 Mar;48(3):445-51
references: 15729581
references: Nature. 2012 Oct 4;490(7418):55-60
references: 23023125
references: Nature. 2010 Jun 24;465(7301):1079-83
references: 20577213
references: Sci Transl Med. 2009 Nov 11;1(6):6ra14
references: 20368178
references: Nat Immunol. 2002 Jun;3(6):576-82
references: 12006975
references: Nature. 2011 Apr 7;472(7341):57-63
references: 21475195
references: Cell Host Microbe. 2008 Feb 14;3(2):67-76
references: 18312841
references: J Mol Med (Berl). 2009 May;87(5):451-4
references: 19219418
references: Nat Immunol. 2011 Aug 28;12(10):941-8
references: 21874025
references: Nat Rev Immunol. 2008 Jun;8(6):421-34
references: 18483500
references: Am J Physiol Endocrinol Metab. 2012 Apr 15;302(8):E961-71
references: 22318945
references: Nat Immunol. 2001 Jul;2(7):625-31
references: 11429547
references: Cell. 2009 Oct 30;139(3):485-98
references: 19836068
references: J Clin Invest. 1995 Jul;96(1):158-62
references: 7615786
references: J Immunol. 2003 Jun 15;170(12):6172-82
references: 12794148
references: Nat Immunol. 2012 Oct;13(10):947-53
references: 22922363
references: Science. 1994 Apr 29;264(5159):707-10
references: 8171323
references: Infect Immun. 2008 Sep;76(9):4241-50
references: 18625738