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Innate Immunity and Metabolic Inflammation

Prof. Chavakis

Prof. Dr. med. Triantafyllos Chavakis

Group Leader


Research Focus

The scientific focus of the group of Prof. Chavakis is in the field of Innate Immunity and metabolic inflammation. We aim at identifying inflammatory mechanisms that are involved in the regulation of acute as well as of chronic inflammation in the context of metabolic-inflammatory pathologies (type 2 diabetes, Non-Alcoholic Fatty Liver disease), inflammatory bone loss and cancer.

At the molecular level, our group studies: (a) The molecular mechanisms governing leukocyte recruitment and activation in the course of inflammation as well as the mechanisms involved in resolution of inflammation. (b) The regulation of innate immune cell generation (myelopoiesis) in the bone marrow. (c) The mechanisms of the crosstalk between inflammation and metabolism at the cellular and systemic organism level. For instance, we analyze the role inflammation in the adipose tissue and the liver in the context of obesity.

 

Specific expertise

Inflammation / Innate Immunity:

  • Leukocyte adhesion and recruitment
  • Integrins
  • Trained Immunity
  • Hematopoiesis / Myelopoiesis
  • Tumor Immunology
  • Bone Inflammation

Metabolic Inflammation

  • Obesity / Adipose tissue inflammation / Type 2 Diabetes
  • Non-Alcoholic Fatty Liver Disease (NAFLD)
  • Cell metabolism

Funding

Lab Members

Prof. Dr. Chavakis, TriantafyllosGroup leader
Dr. Anjanappa, RaghavendraPostdoc
Dr. Chung, Kyoung-JinSenior Scientist
Gebler, JanineTechnician
Dr. Gembardt, StephanieScientific Coordinator
Gercken, BettinaTechnician
Großklaus, SylviaLabmanager
Kalafati, LydiaPhD student
Dr. Kim, Dong-YoungPostdoc
Dr. Nagai, KosukePostdoc
Dr. Nati, MarinaPostdoc
Prucnal, MartaTechnician
Pyrina, IrynaPhD student
Soto, AndresPhD student
Dr. Subramanian, PallaviPostdoc
Dr. Trmaglio, GiuliaPostdoc

Selected Publications

  • Alissafi, T, Kalafati, L, Lazari, M, Filia, A, Kloukina, I, Manifava, M, Lim, J H, Alexaki, V I, Ktistakis, N T, Doskas, T, Garinis, G A, Chavakis, T, Boumpas, D T and Verginis, P. Mitochondrial Oxidative Damage Underlies Regulatory T Cell Defects in Autoimmunity. Cell Metab32: 591-604 e7 (2020)
  • Hatzioannou, A, Banos, A, Sakelaropoulos, T, Fedonidis, C, Vidali, M S, Kohne, M, Handler, K, Boon, L, Henriques, A, Koliaraki, V, Georgiadis, P, Zoidakis, J, Termentzi, A, Beyer, M, Chavakis, T, Boumpas, D, Tsirigos, A and Verginis, P. An intrinsic role of IL-33 in Treg cell-mediated tumor immunoevasion. Nat Immunol21: 75-85 (2020)
  • Kalafati, L, Kourtzelis, I, Schulte-Schrepping, J, Li, X, Hatzioannou, A, Grinenko, T, Hagag, E, Sinha, A, Has, C, Dietz, S, de Jesus Domingues, A M, Nati, M, Sormendi, S, Neuwirth, A, Chatzigeorgiou, A, Ziogas, A, Lesche, M, Dahl, A, Henry, I, Subramanian, P, Wielockx, B, Murray, P, Mirtschink, P, Chung, K J, Schultze, J L, Netea, M G, Hajishengallis, G, Verginis, P, Mitroulis, I and Chavakis, T. Innate Immune Training of Granulopoiesis Promotes Anti-tumor Activity. Cell183: 771-785 e12 (2020)
  • Li, X, Colamatteo, A, Kalafati, L, Kajikawa, T, Wang, H, Lim, J H, Bdeir, K, Chung, K J, Yu, X, Fusco, C, Porcellini, A, De Simone, S, Matarese, G, Chavakis, T, De Rosa, V and Hajishengallis, G. The DEL-1/beta3 integrin axis promotes regulatory T cell responses during inflammation resolution. J Clin Invest130: 6261-6277 (2020)
  • Moorlag, S, Rodriguez-Rosales, Y A, Gillard, J, Fanucchi, S, Theunissen, K, Novakovic, B, de Bont, C M, Negishi, Y, Fok, E T, Kalafati, L, Verginis, P, Mourits, V P, Koeken, V, de Bree, L C J, Pruijn, G J M, Fenwick, C, van Crevel, R, Joosten, L A B, Joosten, I, Koenen, H, Mhlanga, M M, Diavatopoulos, D A, Chavakis, T and Netea, M G. BCG Vaccination Induces Long-Term Functional Reprogramming of Human Neutrophils. Cell Rep33: 108387 (2020)
  • Chavakis, T, Mitroulis, I and Hajishengallis, G. Hematopoietic progenitor cells as integrative hubs for adaptation to and fine-tuning of inflammation. Nat Immunol20: 802-811 (2019)
  • Kourtzelis, I, Li, X, Mitroulis, I, Grosser, D, Kajikawa, T, Wang, B, Grzybek, M, von Renesse, J, Czogalla, A, Troullinaki, M, Ferreira, A, Doreth, C, Ruppova, K, Chen, L S, Hosur, K, Lim, J H, Chung, K J, Grossklaus, S, Tausche, A K, Joosten, L A B, Moutsopoulos, N M, Wielockx, B, Castrillo, A, Korostoff, J M, Coskun, U, Hajishengallis, G and Chavakis, T. DEL-1 promotes macrophage efferocytosis and clearance of inflammation. Nat Immunol20: 40-49 (2019)
  • Wang, B, Lim, J H, Kajikawa, T, Li, X, Vallance, B A, Moutsopoulos, N M, Chavakis, T and Hajishengallis, G. Macrophage beta2-Integrins Regulate IL-22 by ILC3s and Protect from Lethal Citrobacter rodentium-Induced Colitis. Cell Rep26: 1614-1626 e5 (2019)
  • Mitroulis, I, Ruppova, K, Wang, B, Chen, L S, Grzybek, M, Grinenko, T, Eugster, A, Troullinaki, M, Palladini, A, Kourtzelis, I, Chatzigeorgiou, A, Schlitzer, A, Beyer, M, Joosten, L A B, Isermann, B, Lesche, M, Petzold, A, Simons, K, Henry, I, Dahl, A, Schultze, J L, Wielockx, B, Zamboni, N, Mirtschink, P, Coskun, U, Hajishengallis, G, Netea, M G and Chavakis, T. Modulation of Myelopoiesis Progenitors Is an Integral Component of Trained Immunity. Cell172: 147-161 e12 (2018)
  • Chung, K J, Chatzigeorgiou, A, Economopoulou, M, Garcia-Martin, R, Alexaki, V I, Mitroulis, I, Nati, M, Gebler, J, Ziemssen, T, Goelz, S E, Phieler, J, Lim, J H, Karalis, K P, Papayannopoulou, T, Bluher, M, Hajishengallis, G and Chavakis, T. A self-sustained loop of inflammation-driven inhibition of beige adipogenesis in obesity. Nat Immunol18: 654-664 (2017)
  • Mitroulis, I, Chen, L S, Singh, R P, Kourtzelis, I, Economopoulou, M, Kajikawa, T, Troullinaki, M, Ziogas, A, Ruppova, K, Hosur, K, Maekawa, T, Wang, B, Subramanian, P, Tonn, T, Verginis, P, von Bonin, M, Wobus, M, Bornhauser, M, Grinenko, T, Di Scala, M, Hidalgo, A, Wielockx, B, Hajishengallis, G and Chavakis, T. Secreted protein Del-1 regulates myelopoiesis in the hematopoietic stem cell niche. J Clin Invest127: 3624-3639 (2017)
  • Gobel, K, Pankratz, S, Asaridou, C M, Herrmann, A M, Bittner, S, Merker, M, Ruck, T, Glumm, S, Langhauser, F, Kraft, P, Krug, T F, Breuer, J, Herold, M, Gross, C C, Beckmann, D, Korb-Pap, A, Schuhmann, M K, Kuerten, S, Mitroulis, I, Ruppert, C, Nolte, M W, Panousis, C, Klotz, L, Kehrel, B, Korn, T, Langer, H F, Pap, T, Nieswandt, B, Wiendl, H, Chavakis, T, Kleinschnitz, C and Meuth, S G. Blood coagulation factor XII drives adaptive immunity during neuroinflammation via CD87-mediated modulation of dendritic cells. Nat Commun7: 11626 (2016)
  • Choi, E Y, Lim, J H, Neuwirth, A, Economopoulou, M, Chatzigeorgiou, A, Chung, K J, Bittner, S, Lee, S H, Langer, H, Samus, M, Kim, H, Cho, G S, Ziemssen, T, Bdeir, K, Chavakis, E, Koh, J Y, Boon, L, Hosur, K, Bornstein, S R, Meuth, S G, Hajishengallis, G and Chavakis, T. Developmental endothelial locus-1 is a homeostatic factor in the central nervous system limiting neuroinflammation and demyelination. Mol Psychiatry20: 880-888 (2015)
  • Maekawa, T, Hosur, K, Abe, T, Kantarci, A, Ziogas, A, Wang, B, Van Dyke, T E, Chavakis, T and Hajishengallis, G. Antagonistic effects of IL-17 and D-resolvins on endothelial Del-1 expression through a GSK-3beta-C/EBPbeta pathway. Nat Commun6: 8272 (2015)
  • Pruenster, M, Kurz, A R, Chung, K J, Cao-Ehlker, X, Bieber, S, Nussbaum, C F, Bierschenk, S, Eggersmann, T K, Rohwedder, I, Heinig, K, Immler, R, Moser, M, Koedel, U, Gran, S, McEver, R P, Vestweber, D, Verschoor, A, Leanderson, T, Chavakis, T, Roth, J, Vogl, T and Sperandio, M. Extracellular MRP8/14 is a regulator of beta2 integrin-dependent neutrophil slow rolling and adhesion. Nat Commun6: 6915 (2015)
  • Shin, J, Maekawa, T, Abe, T, Hajishengallis, E, Hosur, K, Pyaram, K, Mitroulis, I, Chavakis, T and Hajishengallis, G. DEL-1 restrains osteoclastogenesis and inhibits inflammatory bone loss in nonhuman primates. Sci Transl Med7: 307ra155 (2015)
  • Weber, G F, Chousterman, B G, He, S, Fenn, A M, Nairz, M, Anzai, A, Brenner, T, Uhle, F, Iwamoto, Y, Robbins, C S, Noiret, L, Maier, S L, Zonnchen, T, Rahbari, N N, Scholch, S, Klotzsche-von Ameln, A, Chavakis, T, Weitz, J, Hofer, S, Weigand, M A, Nahrendorf, M, Weissleder, R and Swirski, F K. Interleukin-3 amplifies acute inflammation and is a potential therapeutic target in sepsis. Science347: 1260-5 (2015)
  • Chatzigeorgiou, A, Chung, K J, Garcia-Martin, R, Alexaki, V I, Klotzsche-von Ameln, A, Phieler, J, Sprott, D, Kanczkowski, W, Tzanavari, T, Bdeir, M, Bergmann, S, Cartellieri, M, Bachmann, M, Nikolakopoulou, P, Androutsellis-Theotokis, A, Siegert, G, Bornstein, S R, Muders, M H, Boon, L, Karalis, K P, Lutgens, E and Chavakis, T. Dual role of B7 costimulation in obesity-related nonalcoholic steatohepatitis and metabolic dysregulation. Hepatology60: 1196-210 (2014)
  • Chatzigeorgiou, A, Seijkens, T, Zarzycka, B, Engel, D, Poggi, M, van den Berg, S, van den Berg, S, Soehnlein, O, Winkels, H, Beckers, L, Lievens, D, Driessen, A, Kusters, P, Biessen, E, Garcia-Martin, R, Klotzsche-von Ameln, A, Gijbels, M, Noelle, R, Boon, L, Hackeng, T, Schulte, K M, Xu, A, Vriend, G, Nabuurs, S, Chung, K J, Willems van Dijk, K, Rensen, P C, Gerdes, N, de Winther, M, Block, N L, Schally, A V, Weber, C, Bornstein, S R, Nicolaes, G, Chavakis, T and Lutgens, E. Blocking CD40-TRAF6 signaling is a therapeutic target in obesity-associated insulin resistance. Proc Natl Acad Sci U S A111: 2686-91 (2014)
  • Phieler, J, Chung, K J, Chatzigeorgiou, A, Klotzsche-von Ameln, A, Garcia-Martin, R, Sprott, D, Moisidou, M, Tzanavari, T, Ludwig, B, Baraban, E, Ehrhart-Bornstein, M, Bornstein, S R, Mziaut, H, Solimena, M, Karalis, K P, Economopoulou, M, Lambris, J D and Chavakis, T. The complement anaphylatoxin C5a receptor contributes to obese adipose tissue inflammation and insulin resistance. J Immunol191: 4367-74 (2013)
  • Eskan, M A, Jotwani, R, Abe, T, Chmelar, J, Lim, J H, Liang, S, Ciero, P A, Krauss, J L, Li, F, Rauner, M, Hofbauer, L C, Choi, E Y, Chung, K J, Hashim, A, Curtis, M A, Chavakis, T and Hajishengallis, G. The leukocyte integrin antagonist Del-1 inhibits IL-17-mediated inflammatory bone loss. Nat Immunol13: 465-73 (2012)
  • Langer, H F, Choi, E Y, Zhou, H, Schleicher, R, Chung, K J, Tang, Z, Gobel, K, Bdeir, K, Chatzigeorgiou, A, Wong, C, Bhatia, S, Kruhlak, M J, Rose, J W, Burns, J B, Hill, K E, Qu, H, Zhang, Y, Lehrmann, E, Becker, K G, Wang, Y, Simon, D I, Nieswandt, B, Lambris, J D, Li, X, Meuth, S G, Kubes, P and Chavakis, T. Platelets contribute to the pathogenesis of experimental autoimmune encephalomyelitis. Circ Res110: 1202-10 (2012)
  • Langer, H F, Orlova, V V, Xie, C, Kaul, S, Schneider, D, Lonsdorf, A S, Fahrleitner, M, Choi, E Y, Dutoit, V, Pellegrini, M, Grossklaus, S, Nawroth, P P, Baretton, G, Santoso, S, Hwang, S T, Arnold, B and Chavakis, T. A novel function of junctional adhesion molecule-C in mediating melanoma cell metastasis. Cancer Res71: 4096-105 (2011)
  • Langer, H F, Chung, K J, Orlova, V V, Choi, E Y, Kaul, S, Kruhlak, M J, Alatsatianos, M, DeAngelis, R A, Roche, P A, Magotti, P, Li, X, Economopoulou, M, Rafail, S, Lambris, J D and Chavakis, T. Complement-mediated inhibition of neovascularization reveals a point of convergence between innate immunity and angiogenesis. Blood116: 4395-403 (2010)
  • Wolf, R, Mascia, F, Dharamsi, A, Howard, O M, Cataisson, C, Bliskovski, V, Winston, J, Feigenbaum, L, Lichti, U, Ruzicka, T, Chavakis, T and Yuspa, S H. Gene from a psoriasis susceptibility locus primes the skin for inflammation. Sci Transl Med2: 61ra90 (2010)
  • Economopoulou, M, Langer, H F, Celeste, A, Orlova, V V, Choi, E Y, Ma, M, Vassilopoulos, A, Callen, E, Deng, C, Bassing, C H, Boehm, M, Nussenzweig, A and Chavakis, T. Histone H2AX is integral to hypoxia-driven neovascularization. Nat Med15: 553-8 (2009)
  • Choi, E Y, Chavakis, E, Czabanka, M A, Langer, H F, Fraemohs, L, Economopoulou, M, Kundu, R K, Orlandi, A, Zheng, Y Y, Prieto, D A, Ballantyne, C M, Constant, S L, Aird, W C, Papayannopoulou, T, Gahmberg, C G, Udey, M C, Vajkoczy, P, Quertermous, T, Dimmeler, S, Weber, C and Chavakis, T. Del-1, an endogenous leukocyte-endothelial adhesion inhibitor, limits inflammatory cell recruitment. Science322: 1101-4 (2008)
  • Choi, E Y, Orlova, V V, Fagerholm, S C, Nurmi, S M, Zhang, L, Ballantyne, C M, Gahmberg, C G and Chavakis, T. Regulation of LFA-1-dependent inflammatory cell recruitment by Cbl-b and 14-3-3 proteins. Blood111: 3607-14 (2008)
  • Orlova, V V, Choi, E Y, Xie, C, Chavakis, E, Bierhaus, A, Ihanus, E, Ballantyne, C M, Gahmberg, C G, Bianchi, M E, Nawroth, P P and Chavakis, T. A novel pathway of HMGB1-mediated inflammatory cell recruitment that requires Mac-1-integrin. EMBO J26: 1129-39 (2007)
  • Orlova, V V, Economopoulou, M, Lupu, F, Santoso, S and Chavakis, T. Junctional adhesion molecule-C regulates vascular endothelial permeability by modulating VE-cadherin-mediated cell-cell contacts. J Exp Med203: 2703-14 (2006)