Research Overview

The Winau lab studies diverse aspects of antigen presentation, a process pivotal for activation of T-lymphocytes. Winau and colleagues investigate three principal pillars of antigen presentation including helper molecules of processing (saposins, e.g.), entire presentation pathways (cross-priming, NKT cell activation), and the biology of antigen presenting cells (dendritic cells, stellate cells).

Saposins are small proteins located in the lysosome and are involved in lipid metabolism. We demonstrated that saposin C is able to extract lipid antigens from intralysosomal membranes and additionally is capable of binding to CD1b. Thus, saposins facilitate loading of lipid antigens on CD1 molecules for the activation of CD1-restricted T cells which play an important role in tuberculosis but also in other infectious diseases and pathological conditions. Moreover, saposins are involved in processing of apoptotic bodies. Currently our group investigates the precise mechanism as to how saposins mediate antigen delivery by disintegration of apoptotic vesicles. Since saposins are able to interact with lipid bilayers leading to membrane destruction, a recent project examines the possible antibiotic impact of saposins on bacterial cell walls.

NKT cells represent a lymphocyte subset implicated in immune regulation mainly through rapid burst of cytokines such as IFN-γ and IL-4 thereby imprinting downstream immune responses. They are associated with pathological conditions including cancer, autoimmunity and infection. In addition to diverse exogenous ligands including alpha-galactosylceramide (α-GalCer), NKT cells react with the endogenous lipid antigen isoglobotrihexosylceramide (iGb3). Because antigenicity of iGb3 is comparable to the nominal antigen α-GalCer, we search for control mechanisms avoiding overstimulation of NKT cells. Our group investigates the regulated availability of the endogenous lipid antigen for NKT cells dependent on lysosomal α-galactosidase activity.

Hepatic stellate cells (or Ito cells) are star-shaped cells located in the liver, and they mediate a multitude of primarily non-immunological functions. They play an essential role in the metabolism of vitamin A and store 80% of total body retinol. Upon activation, stellate cells differentiate into myofibroblasts for production of extracellular matrix, leading to liver fibrosis. Recently, our group demonstrated that hepatic stellate cells perform potent antigen presentation stimulating NKT cells as well as CD8 and CD4 T cells. Additionally, stellate cells induced protective immunity against bacterial infection. Currently, we establish in vivo models for stellate cell depletion in order to investigate the impact of stellate cells on T cell instruction and differentiation mediated by vitamin A-derived retinoic acid.

About Florian Winau

Dr. Florian Winau studies diverse aspects of antigen presentation and T cell biology. He is especially interested in the role of lipids in Immunology, acting as antigens or regulators of immune responses.

Dr. Winau received his M.D. from the Charité Humboldt University in Berlin, Germany. He received post-doctoral trining at the Max-Planck-Institute for Infection Biology in Berlin, before establishing his laboratory at Harvard Medical School.

Researcher Services

Researcher Areas

  • Immune Defense
  • Lipid presentation and inflammatory disease
  • Regulation of membrane composition and T cell exhaustion
  • Tissue-specific immunity

Research Departments

Research Divisions

Researcher Programs

Researcher Labs

PUBLICATIONS

Publications powered by Harvard Catalyst Profiles

  1. Beyaz S, Kim JH, Pinello L, Xifaras ME, Hu Y, Huang J, Kerenyi MA, Das PP, Barnitz RA, Herault A, Dogum R, Haining WN, Yilmaz ÖH, Passegue E, Yuan GC, Orkin SH, Winau F. The histone demethylase UTX regulates the lineage-specific epigenetic program of invariant natural killer T cells. Nat Immunol. 2017 02; 18(2):184-195. View abstract
  2. Hu Y, Kim JH, He K, Wan Q, Kim J, Flach M, Kirchhausen T, Vortkamp A, Winau F. Scramblase TMEM16F terminates T cell receptor signaling to restrict T cell exhaustion. J Exp Med. 2016 11 14; 213(12):2759-2772. View abstract
  3. Kim JH, Hu Y, Yongqing T, Kim J, Hughes VA, Le Nours J, Marquez EA, Purcell AW, Wan Q, Sugita M, Rossjohn J, Winau F. CD1a on Langerhans cells controls inflammatory skin disease. Nat Immunol. 2016 10; 17(10):1159-66. View abstract
  4. Kim J, Kim JH, Winau F. Thinking inside the box: endogenous a-anomeric lipid antigens. Immunity. 2014 Oct 16; 41(4):505-6. View abstract
  5. Maschmeyer P, Flach M, Winau F. Seven steps to stellate cells. J Vis Exp. 2011 May 10; (51). View abstract
  6. Darmoise A, Teneberg S, Bouzonville L, Brady RO, Beck M, Kaufmann SH, Winau F. Lysosomal alpha-galactosidase controls the generation of self lipid antigens for natural killer T cells. Immunity. 2010 Aug 27; 33(2):216-28. View abstract
  7. Darmoise A, Maschmeyer P, Winau F. The immunological functions of saposins. Adv Immunol. 2010; 105:25-62. View abstract
  8. Lotter H, González-Roldán N, Lindner B, Winau F, Isibasi A, Moreno-Lafont M, Ulmer AJ, Holst O, Tannich E, Jacobs T. Natural killer T cells activated by a lipopeptidophosphoglycan from Entamoeba histolytica are critically important to control amebic liver abscess. PLoS Pathog. 2009 May; 5(5):e1000434. View abstract
  9. Raftery MJ, Winau F, Giese T, Kaufmann SH, Schaible UE, Schönrich G. Viral danger signals control CD1d de novo synthesis and NKT cell activation. Eur J Immunol. 2008 Mar; 38(3):668-79. View abstract
  10. Raftery MJ, Hitzler M, Winau F, Giese T, Plachter B, Kaufmann SH, Schönrich G. Inhibition of CD1 antigen presentation by human cytomegalovirus. J Virol. 2008 May; 82(9):4308-19. View abstract
  11. Winau F, Quack C, Darmoise A, Kaufmann SH. Starring stellate cells in liver immunology. Curr Opin Immunol. 2008 Feb; 20(1):68-74. View abstract
  12. Winau F, Hegasy G, Weiskirchen R, Weber S, Cassan C, Sieling PA, Modlin RL, Liblau RS, Gressner AM, Kaufmann SH. Ito cells are liver-resident antigen-presenting cells for activating T cell responses. Immunity. 2007 Jan; 26(1):117-29. View abstract
  13. Raftery MJ, Winau F, Kaufmann SH, Schaible UE, Schönrich G. CD1 antigen presentation by human dendritic cells as a target for herpes simplex virus immune evasion. J Immunol. 2006 Nov 01; 177(9):6207-14. View abstract
  14. Wunder C, Churin Y, Winau F, Warnecke D, Vieth M, Lindner B, Zähringer U, Mollenkopf HJ, Heinz E, Meyer TF. Cholesterol glucosylation promotes immune evasion by Helicobacter pylori. Nat Med. 2006 Sep; 12(9):1030-8. View abstract
  15. Winau F, Weber S, Sad S, de Diego J, Hoops SL, Breiden B, Sandhoff K, Brinkmann V, Kaufmann SH, Schaible UE. Apoptotic vesicles crossprime CD8 T cells and protect against tuberculosis. Immunity. 2006 Jan; 24(1):105-17. View abstract
  16. Kaufmann SH, Winau F. From bacteriology to immunology: the dualism of specificity. Nat Immunol. 2005 Nov; 6(11):1063-6. View abstract
  17. Kolter T, Winau F, Schaible UE, Leippe M, Sandhoff K. Lipid-binding proteins in membrane digestion, antigen presentation, and antimicrobial defense. J Biol Chem. 2005 Dec 16; 280(50):41125-8. View abstract
  18. Winau F, Hegasy G, Kaufmann SH, Schaible UE. No life without death--apoptosis as prerequisite for T cell activation. Apoptosis. 2005 Aug; 10(4):707-15. View abstract
  19. Winau F, Sponaas AM, Weber S, Schwierzeck V, Winter R, Hurwitz R, Kaufmann SH. Scant activation of CD8 T cells by antigen loaded on heat shock protein. Eur J Immunol. 2005 Apr; 35(4):1046-55. View abstract
  20. Winau F, Kaufmann SH, Schaible UE. Apoptosis paves the detour path for CD8 T cell activation against intracellular bacteria. Cell Microbiol. 2004 Jul; 6(7):599-607. View abstract
  21. Winau F, Westphal O, Winau R. Paul Ehrlich--in search of the magic bullet. Microbes Infect. 2004 Jul; 6(8):786-9. View abstract
  22. Winau F, Schwierzeck V, Hurwitz R, Remmel N, Sieling PA, Modlin RL, Porcelli SA, Brinkmann V, Sugita M, Sandhoff K, Kaufmann SH, Schaible UE. Saposin C is required for lipid presentation by human CD1b. Nat Immunol. 2004 Feb; 5(2):169-74. View abstract
  23. Schaible UE, Winau F, Sieling PA, Fischer K, Collins HL, Hagens K, Modlin RL, Brinkmann V, Kaufmann SH. Apoptosis facilitates antigen presentation to T lymphocytes through MHC-I and CD1 in tuberculosis. Nat Med. 2003 Aug; 9(8):1039-46. View abstract
  24. Winau F, Winau R. Emil von Behring and serum therapy. Microbes Infect. 2002 Feb; 4(2):185-8. View abstract