title: Rapid linkage of innate immunological signals to adaptive immunity by the brain-fat axis.
abstract: Innate immunological signals induced by pathogen- and/or damage-associated molecular patterns are essential for adaptive immune responses, but it is unclear if the brain has a role in this process. Here we found that while the abundance of tumor-necrosis factor (TNF) quickly increased in the brain of mice following bacterial infection, intra-brain delivery of TNF mimicked bacterial infection to rapidly increase the number of peripheral lymphocytes, especially in the spleen and fat. Studies of various mouse models revealed that hypothalamic responses to TNF were accountable for this increase in peripheral lymphocytes in response to bacterial infection. Finally, we found that hypothalamic induction of lipolysis mediated the brain's action in promoting this increase in the peripheral adaptive immune response. Thus, the brain-fat axis is important for rapid linkage of innate immunity to adaptive immunity.
authors.affiliation: 1] Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA. [2] Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, USA. [3] Institute of Aging, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Min Soo
authors.initials: MS
authors.lastname: Kim
authors.affiliation: 1] Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA. [2] Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, USA. [3] Institute of Aging, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Jingqi
authors.initials: J
authors.lastname: Yan
authors.affiliation: 1] Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA. [2] Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, USA. [3] Institute of Aging, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Wenhe
authors.initials: W
authors.lastname: Wu
authors.affiliation: 1] Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA. [2] Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, USA. [3] Institute of Aging, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Guo
authors.initials: G
authors.lastname: Zhang
authors.affiliation: 1] Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA. [2] Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, USA. [3] Institute of Aging, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Yalin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 1] Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, New York, USA. [2] Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, USA. [3] Institute of Aging, Albert Einstein College of Medicine, Bronx, New York, USA.
authors.forename: Dongsheng
authors.initials: D
authors.lastname: Cai
mesh_terms: D056704:Adaptive Immunity; D000273:Adipose Tissue / Q000276:immunology*; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000382:microbiology; D002452:Cell Count; D002478:Cells, Cultured; D005227:Fatty Acids / Q000097:blood; D007031:Hypothalamus / Q000276:immunology* / Q000382:microbiology; D007113:Immunity, Innate; D008066:Lipolysis / Q000276:immunology; D008088:Listeriosis / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage* / Q000097:blood / Q000134:cerebrospinal fluid
chemical_list: D005227:Fatty Acids; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha
references.citation: Nat Rev Microbiol. 2006 Jun;4(6):423-34
references.pmid: 16710323
references.citation: Nat Med. 2011 Jul;17(7):883-7
references.pmid: 21642978
references.citation: Am J Pathol. 1999 Dec;155(6):2145-52
references.pmid: 10595943
references.citation: Rev Immunogenet. 2000;2(3):359-73
references.pmid: 11256745
references.citation: Annu Rev Immunol. 2002;20:197-216
references.pmid: 11861602
references.citation: Am J Physiol Endocrinol Metab. 2003 Oct;285(4):E917-25
references.pmid: 12799315
references.citation: Mol Immunol. 2004 Feb;40(12):845-59
references.pmid: 14698223
references.citation: Nat Immunol. 2004 Oct;5(10):971-4
references.pmid: 15454919
references.citation: Nat Rev Immunol. 2004 Oct;4(10):812-23
references.pmid: 15459672
references.citation: J Clin Invest. 2012 Jan;122(1):153-62
references.pmid: 22201683
references.citation: Nat Cell Biol. 2012 Oct;14(10):999-1012
references.pmid: 22940906
references.citation: J Exp Biol. 2013 Jan 1;216(Pt 1):84-98
references.pmid: 23225871
references.citation: Proc Natl Acad Sci U S A. 2013 Apr 9;110(15):6193-8
references.pmid: 23530205
references.citation: Nature. 2013 May 9;497(7448):211-6
references.pmid: 23636330
references.citation: Proc Natl Acad Sci U S A. 2013 Jun 18;110(25):10306-11
references.pmid: 23733958
references.citation: Nat Med. 2014 Sep;20(9):1001-8
references.pmid: 25086906
references.citation: Prog Brain Res. 1992;91:219-33
references.pmid: 1410407
references.citation: Endocrinology. 1993 Nov;133(5):2255-62
references.pmid: 8404678
references.citation: J Immunol. 1998 Jan 15;160(2):943-52
references.pmid: 9551933
references.citation: Am J Physiol. 1998 Nov;275(5 Pt 2):R1488-93
references.pmid: 9791065
references.citation: Endocrinology. 2005 May;146(5):2157-64
references.pmid: 15677756
references.citation: J Clin Invest. 2005 Apr;115(4):951-8
references.pmid: 15761497
references.citation: Circ Res. 2005 May 13;96(9):939-49
references.pmid: 15890981
references.citation: Nat Rev Neurosci. 2005 Oct;6(10):775-86
references.pmid: 16163382
references.citation: Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):5219-23
references.pmid: 16549778
references.citation: J Biol Chem. 2011 Sep 16;286(37):32324-32
references.pmid: 21784844
references.citation: Biochem Biophys Res Commun. 2006 Aug 4;346(3):721-6
references.pmid: 16782068
references.citation: J Exp Med. 2006 Jul 10;203(7):1623-8
references.pmid: 16785311
references.citation: J Clin Invest. 2006 Nov;116(11):3015-25
references.pmid: 17053832
references.citation: Nature. 2006 Dec 14;444(7121):860-7
references.pmid: 17167474
references.citation: Curr Opin Immunol. 2007 Feb;19(1):1-3
references.pmid: 17157490
references.citation: Circulation. 2007 Feb 27;115(8):1029-38
references.pmid: 17296858
references.citation: Trends Immunol. 2007 Oct;28(10):429-36
references.pmid: 17845865
references.citation: J Biol Chem. 2007 Nov 30;282(48):35279-92
references.pmid: 17916553
references.citation: Nat Med. 2008 Jun;14(6):667-75
references.pmid: 18516053
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):11008-13
references.pmid: 18669662
references.citation: Endocrinology. 2008 Oct;149(10):5209-18
references.pmid: 18583419
references.citation: Cell. 2008 Oct 3;135(1):61-73
references.pmid: 18854155
references.citation: J Biol Chem. 2009 Feb 27;284(9):5915-26
references.pmid: 19122198
references.citation: Am J Physiol Endocrinol Metab. 2009 May;296(5):E1003-12
references.pmid: 19116375
references.citation: Nature. 2009 Jul 2;460(7251):103-7
references.pmid: 19494812
references.citation: Nat Med. 2009 Aug;15(8):930-9
references.pmid: 19633656
references.citation: Nat Med. 2009 Aug;15(8):914-20
references.pmid: 19633658
references.citation: Curr Opin Lipidol. 2009 Oct;20(5):379-85
references.pmid: 19625959
references.citation: Cell Metab. 2009 Nov;10(5):419-29
references.pmid: 19883619
references.citation: Trends Endocrinol Metab. 2011 Jan;22(1):16-23
references.pmid: 20888253
references.citation: Proc Natl Acad Sci U S A. 2011 Feb 15;108(7):2939-44
references.pmid: 21282643
references.citation: Eur J Neurosci. 2011 Mar;33(6):1139-51
references.pmid: 21395858
references.citation: Science. 2011 May 6;332(6030):729-32
references.pmid: 21474712