- Dendritic cells
- Type 2 immune responses
After obtaining my Masters Degree at in 2005 at the University of Amsterdam, specializing on host-pathogen interactions, I started my PhD at the department of Parasitology at the Leiden University Medical Center (LUMC) in the group of Prof. Dr. Maria Yazdanbakhsh. During my PhD I studied the immunomodulatory effects of molecules derived from the widespread tropical parasitic worm, Schistosoma, on dendritic cells (DCs) by performing both in vitro studies as well as field studies in Africa. Following my PhD In 2010, I started as a postdoctoral fellow, to work in the emerging field of immunometabolism, in the group of Prof. Dr. E.J. Pearce at the School of Medicine of Washington University, St Louis, Missouri, USA. In his laboratory, I focused on the cellular metabolic requirements for DC activation and their immune-priming capacity. Through support from a VENI fellowship from NWO, a Marie Curie Career Integration Grant and a Gisela Thier Fellowship from the LUMC, I returned to the department of Parasitology at the LUMC in June 2014, where I am currently working on the metabolic control of the immunoregulatory functions of DCs.
Research interest and funding
DCs are key regulators of both immunity and tolerance by controlling activation and polarization of effector T cells and regulatory T cell responses (Treg). Therefore, there is a major focus on developing approaches to manipulate DC function for immunotherapy. It is well known that changes in cellular activation are coupled to profound changes in cellular metabolism. However, only recently, based on studies with T cells and macrophages, the picture is emerging that manipulation of cellular metabolism can be used to shape immune responses. This field of immunometabolism is rapidly evolving as one of the new frontiers in science. Nonetheless, still little is known about the metabolic processes that support DC activation or about the metabolic requirements for DCs to drive different effector T cell or Treg responses. My research focuses on this novel concept and aims to unravel the metabolic bases for the immune-polarizing properties of DCs, using both human in vitro as well as murine models. Ultimately, the goal is to identify novel metabolism-based strategies for improving DC-based immunotherapy.
Title: Identification and targeting of metabolic pathways in dendritic cells that regulate their immune polarizing function (grant # 91614087)
Marie Curie Career Integration Grant, European Commission
Title: Identification and targeting of metabolic pathways in dendritic cells that regulate their immune polarizing function (grant # 631585)
LUMC Fellowship, Leiden University Medical Center
Title: Metabolic control of dendritic cell-driven T cell polarization: dissecting underlying signals
LUMC Fellowship, Leiden University Medical Center
Title: Understanding how the metabolic microenvironment shapes tolerance: targeting metabolic sensor AMPK in dendritic cells to break the spell
Title: Hitting the sweet spot of dendritic cells and macrophages: Targeting O-GlcNAcylation to shape Type 2 immune responses
Pelgrom LR, Patente TA, Sergushichev A, Esaulova E, Otto F, Ozir-Fazalalikhan A, van der Zande HJP, van der Ham AJ, van der Stel S, Artyomov MN, Everts B. LKB1 expressed in dendritic cells governs the development and expansion of thymus-derived regulatory T cells. Cell Res. 2019 Apr 2.
Kaisar MMM, Ritter M, Del Fresno C, Jónasdóttir HS, van der Ham AJ, Pelgrom LR, Schramm G, Layland LE, Sancho D, Prazeres da Costa C, Giera M, Yazdanbakhsh M, Everts B. Dectin-1/2-induced autocrine PGE2 signaling licenses dendritic cells to prime Th2 responses. PLoS Biol . 2018 Apr 18;16(4):e2005504
Hansen IS, Krabbendam L, Bernink JH, Loayza-Puch F, Hoepel W, van Burgsteden JA, Kuijper EC, Buskens CJ, Bemelman WA, Zaat SAJ, Agami R, Vidarsson G, van den Brink GR, de Jong EC, Wildenberg ME, Baeten DLP, Everts B, den Dunnen J. FcαRI co-stimulation converts human intestinal CD103+ dendritic cells into pro-inflammatory cells through glycolytic reprogramming. Nat Commun. 2018 Feb 28;9(1):863
Kaisar MMM, Pelgrom LR, van der Ham AJ, Yazdanbakhsh M, Everts B. Butyrate Conditions Human Dendritic Cells to Prime Type 1 Regulatory T Cells via both Histone Deacetylase Inhibition and G Protein-Coupled Receptor 109A Signaling. Front Immunol. 2017 Oct 30;8:1429
Thwe PM, Pelgrom L, Cooper R, Beauchamp S, Reisz JA, D'Alessandro A, Everts B, Amiel E. Cell-Intrinsic Glycogen Metabolism Supports Early Glycolytic Reprogramming Required for Dendritic Cell Immune Responses. Cell Metab. 2017 Sep 5;26(3):558-567.e5
Huang SC, Smith AM, Everts B, Colonna M, Pearce EL, Schilling JD, Pearce EJ. Metabolic Reprogramming Mediated by the mTORC2-IRF4 Signaling Axis Is Essential for Macrophage Alternative Activation. Immunity. 2016 Oct 18;45(4):817-830.
Wu D, Sanin DE, Everts B, Chen Q, Qiu J, Buck MD, Patterson A, Smith AM, Chang CH, Liu Z, Artyomov MN, Pearce EL, Cella M, Pearce EJ. Type 1 Interferons Induce Changes in Core Metabolism that Are Critical for Immune Function. Immunity. 2016 Jun 21;44(6):1325-36
Everts B, Tussiwand R, Dreesen L, Fairfax KC, Huang SC, Smith AM, O'Neill CM, Lam WY, Edelson BT, Urban JF Jr, Murphy KM, Pearce EJ. Migratory CD103+ dendritic cells suppress helminth-driven type 2 immunity through constitutive expression of IL-12. J Exp Med. 2016 Jan 11;213(1):35-51
Tussiwand R, Everts B, Grajales-Reyes GE, Kretzer NM, Iwata A, Bagaitkar J, Wu X, Wong R, Anderson DA, Murphy TL, Pearce EJ, Murphy KM. Klf4 Expression in Conventional Dendritic Cells Is Required for T Helper 2 Cell Responses. Immunity. 2015 May 19;42(5):916-928
Jha AK, Huang SC, Sergushichev A, Lampropoulou V, Ivanova Y, Loginicheva E, Chmielewski, Stewart KM, Ashall J, Everts B, Pearce EJ, Driggers EM, Artyomov MN. Network Integration of Parallel Metabolic and Transcriptional Data Reveals Metabolic Modules that Regulate Macrophage Polarization. Immunity. 2015 Mar 17;42(3):419-30.
Pearce EJ, Everts B. Dendritic cell metabolism. Nat Rev Immunol. 2015 Jan;15(1):18-29
Huang SC, Everts B, Ivanova Y, O'Sullivan D, Nascimento M, Smith AM, Beatty W, Love-Gregory L, Lam WY, O'Neill CM, Yan C, Du H, Abumrad NA, Urban JF Jr, Artyomov MN, Pearce EL, Pearce EJ. Cell-intrinsic lysosomal lipolysis is essential for alternative activation of macrophages. Nat Immunol. 2014 Sep;15(9):846-55
Everts B, Amiel E, Huang SC, Smith AM, Chang CH, Lam WY, Redmann V, Freitas TC, Blagih J, van der Windt GJ, Artyomov MN, Jones RG, Pearce EL, Pearce EJ. TLR-driven early glycolytic reprogramming via the kinases TBK1-IKKepsilon supports the anabolic demands of dendritic cell activation. Nat Immunol. 2014 Apr;15(4):323-32
Everts B, Hussaarts L, Driessen NN, Meevissen MH, Schramm G, van der Ham AJ, van der Hoeven B, Scholzen T, Burgdorf S, Mohrs M, Pearce EJ, Hokke CH, Haas H, Smits HH, Yazdanbakhsh M. Schistosome-derived omega-1 drives Th2 polarization by suppressing protein synthesis following internalization by the mannose receptor. J Exp Med. 2012 Sep 24;209(10):1753-67.
Everts B, Amiel E, van der Windt GJ, Freitas TC, Chott R, Yarasheski KE, Pearce EL, Pearce EJ. Commitment to glycolysis sustains survival of NO-producing inflammatory dendritic cells. Blood. 2012 Aug 16;120(7):1422-31.
van der Windt GJ, Everts B, Chang CH, Curtis JD, Freitas TC, Amiel E, Pearce EJ, Pearce EL. Mitochondrial respiratory capacity is a critical regulator of CD8+ T cell memory development. Immunity. 2012 Jan 27;36(1):68-78.
Everts B, Perona-Wright G, Smits HH, Hokke CH, van der Ham AJ, Fitzsimmons CM, Doenhoff MJ, van der Bosch J, Mohrs K, Haas H, Mohrs M, Yazdanbakhsh M, Schramm G. Omega-1, a glycoprotein secreted by Schistosoma mansoni eggs, drives Th2 responses. J Exp Med. 2009 Aug 3;206(8):1673-80.
The complete list of publications can be found at Google Scholar
Leids Universitair Medisch Centrum
2333 ZA Leiden
Tel: +31 71 526 5070
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