Blocking CD40-TRAF6 signaling is a therapeutic target in obesity-associated insulin resistance

Proceedings of the National Academy of Sciences of the United States of America

Volumn 111, Issue 7, 2014, Pages 2686-2691

  Chatzigeorgiou, Antonios ^a,b   Seijkens, Tom ^c   Zarzycka, Barbara ^d   Engel, David ^d   Poggi, Marjorie ^d,e   Van Den Berg, Susan ^c   Van Den Berg, Sjoerd ^f   Soehnlein, Oliver ^c,g   Winkels, Holger ^c,g   Beckers, Linda ^c   Lievens, Dirk ^c,g   Driessen, Ann ^h   Kusters, Pascal ^a   Biessen, Erik ^d   Garcia Martin, Ruben ^a   Ameln, Anne Klotzsche Von ^a   Gijbels, Marion ^c,d,i   Noelle, Randolph ^j,k   Boon, Louis ^l   Hackeng, Tilman ^d   Schulte, Klaus ^m   Xu, Aimin ⁿ   Vriend, Gert ^o   Nabuurs, Sander ^o,p   Chung, Kyoung Jin ^a   Van Dijk, Ko Willems ^f   Rensen, Patrick C N ^f   Gerdes, Norbert ^c,g   De Winther, Menno ^c   Block, Norman L ^q,r   Schally, Andrew V ^q,r   Weber, Christian ^g,s   Bornstein, Stefan R ^a,t   Nicolaes, Gerry ^d   Chavakis, Triantafyllos ^a,b   Lutgens, Esther ^c,g   more..

^a DRESDEN UNIVERSITY OF TECHNOLOGY   (Germany)

^b GERMAN CENTER FOR DIABETES RESEARCH DZD   (Germany)

^c UNIVERSITY OF AMSTERDAM   (Netherlands)

^d MAASTRICHT UNIVERSITY   (Netherlands)

^e INSERM   (France)

^f LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^g LUDWIG MAXIMILIANS UNIVERSITY   (Germany)

^h ANTWERP UNIVERSITY HOSPITAL   (Belgium)

ⁱ MAASTRICHT UNIVERSITY   (Netherlands)

^j DARTMOUTH MEDICAL SCHOOL   (United States)

^k GUY S HOSPITAL   (United Kingdom)

^l BIOCEROS   (Netherlands)

^m KING S COLLEGE HOSPITAL   (United Kingdom)

ⁿ UNIVERSITY OF HONG KONG   (Hong Kong)

^o RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^p Lead Pharma Medicine   (Netherlands)

^q UNIVERSITY OF MIAMI MILLER SCHOOL OF MEDICINE   (United States)

^r VETERANS AFFAIRS MEDICAL CENTER   (United States)

^s DZHK GERMAN CENTRE FOR CARDIOVASCULAR RESEARCH   (Germany)

^t KING'S COLLEGE LONDON   (United Kingdom)

more..

Author keywords

Immunity; Metabolism; Type 2 diabetes

Indexed keywords

6877002; CD40 LIGAND; PROTEIN INHIBITOR; TUMOR NECROSIS FACTOR RECEPTOR ASSOCIATED FACTOR 6; UNCLASSIFIED DRUG;

ADIPOSE TISSUE; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CD8+ T LYMPHOCYTE; CELL PROTECTION; DIET INDUCED OBESITY; DRUG MECHANISM; FATTY LIVER; INSULIN RESISTANCE; INSULIN SENSITIVITY; MACROPHAGE; MALE; MOUSE; NONHUMAN; OBESITY; PRIORITY JOURNAL; WEIGHT GAIN;

IMMUNITY; METABOLISM; TYPE 2 DIABETES;

ADIPOSE TISSUE; ANALYSIS OF VARIANCE; ANIMALS; ANTIGENS, CD40; AZO COMPOUNDS; CALORIMETRY; CD8-POSITIVE T-LYMPHOCYTES; FATTY LIVER; FLOW CYTOMETRY; INSULIN RESISTANCE; LIGANDS; MAGNETIC RESONANCE SPECTROSCOPY; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; OBESITY; REAL-TIME POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; SURFACE PLASMON RESONANCE; TNF RECEPTOR-ASSOCIATED FACTOR 6;

EID: 84894377101     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1400419111     Document Type: Article

References (27)

1. Osborn O, Sears DD, Olefsky JM (2010) Fat-induced inflammation unchecked. Cell Metab 12(6):553-554.
2. Chatzigeorgiou A, Karalis KP, Bornstein SR, Chavakis T (2012) Lymphocytes in obesityrelated adipose tissue inflammation. Diabetologia 55(10):2583-2592.
3. Gregor MF, Hotamisligil GS (2011) Inflammatory mechanisms in obesity. Annu Rev Immunol 29:415-445.
4. Nishimura S, et al. (2009) CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med 15(8):914-920.
5. FeuererM, et al. (2009) Lean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nat Med 15(8):930-939.
6. Osborn O, Olefsky JM (2012) The cellular and signaling networks linking the immune system and metabolism in disease. Nat Med 18(3):363-374.
7. Johnson AMF, Olefsky JM (2013) The origins and drivers of insulin resistance. Cell 152(4):673-684.
8. Foy TM, Aruffo A, Bajorath J, Buhlmann JE, Noelle RJ (1996) Immune regulation by CD40 and its ligand GP39. Annu Rev Immunol 14:591-617.
9. Guldiken SS, et al. (2007) The levels of circulating markers of atherosclerosis and inflammation in subjects with different degrees of body mass index: Soluble CD40 ligand and high-sensitivity C-reactive protein. Thromb Res 119(1):79-84.
10. Poggi M, et al. (2009) The inflammatory receptor CD40 is expressed on human adipocytes: Contribution to crosstalk between lymphocytes and adipocytes. Diabetologia 52(6):1152-1163.
11. Missiou A, et al. (2010) CD40L induces inflammation and adipogenesis in adipose cells-a potential link between metabolic and cardiovascular disease. Thromb Haemost 103(4): 788-796.
12. Poggi M, et al. (2011) CD40L deficiency ameliorates adipose tissue inflammation and metabolic manifestations of obesity in mice. Arterioscler Thromb Vasc Biol 31(10): 2251-2260.
13. Wolf D, et al. (2012) CD40L deficiency ameliorates diet-induced adipose tissue inflammation, but does not protect from insulin resistance and hepatic steatosis in mice. Eur Heart J 33(Abstr Suppl):880.
14. Kawai T, Andrews D, Colvin R, Sachs D, Cosimi A (2000) Thromboembolic complications after treatment with monoclonal antibody against CD40 ligand. Nat Med 6(2): 114 (lett).
15. Kawabe T, et al. (1994) The immune responses in CD40-deficient mice: Impaired immunoglobulin class switching and germinal center formation. Immunity 1(3):167-178.
16. Ahonen C, et al. (2002) The CD40-TRAF6 axis controls affinity maturation and the generation of long-lived plasma cells. Nat Immunol 3(5):451-456.
17. Quezada SA, Jarvinen LZ, Lind EF, Noelle RJ (2004) CD40/CD154 interactions at the interface of tolerance and immunity. Annu Rev Immunol 22:307-328.
18. Engel D, et al. (2009) The immunobiology of CD154-CD40-TRAF interactions in atherosclerosis. Semin Immunol 21(5):308-312.
19. Lumeng CN, Saltiel AR (2011) Inflammatory links between obesity and metabolic disease. J Clin Invest 121(6):2111-2117.
20. Phieler J, et al. (2013) The complement anaphylatoxin C5a receptor contributes to obese adipose tissue inflammation and insulin resistance. J Immunol 191(8): 4367-4374.
21. Lutgens E, et al. (2010) Deficient CD40-TRAF6 signaling in leukocytes prevents atherosclerosis by skewing the immune response toward an antiinflammatory profile. J Exp Med 207(2):391-404.
22. Donners MMPC, et al. (2008) The CD40-TRAF6 axis is the key regulator of the CD40/CD40L system in neointima formation and arterial remodeling. Blood 111(9):4596-4604.
23. Wolf D, et al. (2011) Binding of CD40L to Mac-1's I-domain involves the EQLKKSKTL motif and mediates leukocyte recruitment and atherosclerosis-but does not affect immunity and thrombosis in mice. Circ Res 109(11):1269-1279.
24. Zirlik A, et al. (2007) CD40 ligand mediates inflammation independently of CD40 by interaction with Mac-1. Circulation 115(12):1571-1580.
25. Dong ZM, Gutierrez-Ramos JC, Coxon A, Mayadas TN, Wagner DD (1997) A new class of obesity genes encodes leukocyte adhesion receptors. Proc Natl Acad Sci USA 94(14): 7526-7530.
26. Guo C-A, et al. (2013) CD40 deficiency in mice exacerbates obesity-induced adipose tissue inflammation, hepatic steatosis, and insulin resistance. Am J Physiol Endocrinol Metab 304(9):E951-E963.
27. Beatty GL, et al. (2011) CD40 agonists alter tumor stroma and show efficacy against pancreatic carcinoma in mice and humans. Science 331(6024):1612-1616.