A14

A14: Summary

At sites of inflammation, TH1 and TH17 cells are the major orchestrators of immune-mediated tissue damage. Some of these effector cells retain some degree of plasticity and can acquire an immuno-suppressive function. We hypothesize that the hydrolysis of ATP to ADO by TH1 and TH17 cells contributes to their conversion into regulatory cells. We will use cytokine-reporter mouse models and human cells to assess the role of ADO, CD39 and CD73 in the conversion of effector TH1 and TH17 cells into regulatory T cells, and will address the mechanisms underlying this conversion. Finally, we will assess the in vivo consequences of a loss of ADO signaling in effector T cells in a mouse model of intestinal inflammation.

Prof. Dr. Eva Tolosa

Selected publications

 

  1. Solano ME, Holmes MC, Mittelstadt PR, Chapman KE*, Tolosa E* (2016) Antenatal endogenous and exogenous glucocorticoids and their impact on immune ontogeny and long-term immunity. Semin Immunopathol 38:739-763.
  2. Rissiek A, Baumann I, Cuapio A, ter Haar N, Kolster M, Dodge-Khatami A, Arck PC, Mittrücker HW, Koch-Nolte F, Haag F, Tolosa E (2015) The expression of CD39 on regulatory T cells is genetically driven and further upregulated at sites of inflammation. J Autoimmunity 58:12-20.
  3. Diepenbruck I, Much CC, Krumbholz A, Kolster M, Thieme R, Thieme D, Solano ME, Arck PC, Tolosa E (2013) Effect of prenatal steroid treatment on the developing immune system. J Mol Med (Berl) 91:1293-1302.
  4. Stoeckle C, Quecke P, Rückrich T, Burster T, Reich M, Weber E, Kalbacher H, Driessen C, Melms A, Tolosa E (2012) Cathepsin S dominates autoantigen processing in human thymic dendritic cells. J Autoimmun. 38:332-343.
  5. Gelderblom M, Weymar A, Bernreuther C, Velden J, Arunachalam P, Steinbach K, Orthey E, Arumugam TV, Leypoldt F, Simova O, Thom V, Friese MA, Prinz I, Hölscher C, Glatzel M, Korn T, Gerloff C, Tolosa E, Magnus T (2012) Neutralization of the IL-17 axis diminishes neutrophil invasion and protects from ischemic stroke. Blood 120:3793-3802.
  6. Brucklacher-Waldert V, Stuerner K, Kolster M, Wolthausen J, Tolosa E (2009) Th17 cells display high pathogenic potential and are increased in the CSF of multiple sclerosis patients during relapse. Brain 132:3329-3341.
  7. Brucklacher-Waldert V, Steinbach K, Kolster M, Lioznov M, Hoelscher C, Tolosa E (2009) Phenotypical and functional characterization of human Th17 cells unambiguously identified by surface IL-17A expression. J Immunol 183:5494-5501.
  8. Feger U*, Tolosa E *, Yu-Hwa H*, Biedermann T, Melms A, Wiendl H (2007) HLA-G expression defines a novel regulatory T cell subset present in human peripheral blood and sites of neuroinflammation. Blood 110:568-577 (*shared authorship).
  9. Tolosa E, Li W, Yasuda Y, Wienhold W, Denzin LK, Melms A, Bromme D (2003) Cathepsin V is involved in the degradation of invariant chain in human thymus and is overexpressed in myasthenia gravis. J Clin Invest 112:517-526.

Prof. Nicola Gagliani

Selected publications

 

  1. Brockmann L*, Gagliani N*, Steglich B, Giannou AD, Kempski J, Pelczar P, Geffken M, Mfarrej B, Huber F, Herkel J, Wan YY, Esplugues E, Battaglia M, Krebs CF, Flavell RA, Huber S (2017) IL-10 Receptor Signaling Is Essential for TR1 Cell Function In Vivo. J Immunol 198:1130-1141. *equal contribution
  2. Pelczar P, Witkowski M, Garcia Perez L, Kempski J, Hammel AG, Brockmann L, Kleinschmidt D, Wende S, Haueis C, Bedke T, Witkowski M, Krasemann S, Steurer S, Booth CJ, Busch P, König A, Rauch U, Benten D, Izbicki JR, Rösch T, Lohse AW, Strowig T, Gagliani N*, Flavell RA*, Huber S* (2016) A pathogenic role for T cell–derived IL-22BP in inflammatory bowel disease. Science 354:358362. *equal contribution as last authors
  3. Gagliani N, Amezcua C, Iseppon A, Brockmann L, Xu H, Palm N, de Zoete M, Licona-Limón P, Paiva R, Ching T, Weaver C, Zi X, Fan R, Garmire L, Cotton M, Drier Y, Bernstein B, Geginat J, Stockinger B, Esplugues E, Huber S, Flavell RA (2015) Th17 cells transdifferentiate into regulatory cells during the resolution of inflammatory response. Nature 9:523:221-225.
  4. Gagliani N*, Bo H*, Huber S*, Elinav E*, Flavell RA (2014) The Fire Within: Microbes inflame tumor. Cell 157:776-783. *equal contribution
  5. Gagliani N*, Magnani FC*, Huber S*, Gianolini ME, Pala M, Limona LP, Guo B, De’Broski HR, Bulfone A, Trentini F, Di Serio C, Bacchetta R, Andreani M, Brockmann L, Gregori S, Flavell R, Roncarolo MG (2013) Coexpression of CD49b and LAG-3 identifies human and murine T regulatory type 1 cells. Nat Med 19:739-746. *equal contribution
  6. Gagliani N, Jofra T, Valle A, Stabilini A, Morsiani C, Gregori S, Deng S, Rothstein DR, Atkinson M, Kamanaka M, Flavell RA, Roncarolo MG, Battaglia M (2013) Transplant tolerance to pancreatic islets is initiated in the graft and sustained in the spleen. Am J Transplant 13:1963-1975.
  7. Huber S*, Gagliani N*, Zenewicz ZA, Huber FJ, Bosurgi L, Hu B, Hedl M, Zhang W, O’Connor W, Murphy AJ, David M, Valenzuela DM, Yancopoulos GD, Booth CJ, Cho JH, Ouyang W, Abraham C, Flavell RA (2012) IL-22BP is regulated by the inflammasome and modulates tumorigenesis in the intestine. Nature 491:259-263. *equal contribution
  8. Huber S*, Gagliani N*, Esplugues E*, O’Connor W Jr , Huber FJ, Chaudhry A, Kamanaka M, Kobajashi Y, Booth CJ, Rudensky AY, Battaglia M, Flavell RA (2011) Th17 cells express interleukin-10 receptor and are controlled by Foxp3- and Foxp3+ regulatory CD4+ T cells in an interleukin-10dependent manner. Immunity 34:554-565. *equal contribution
  9. Esplugues E, Huber S, Gagliani N, Hauser A, Town T, Wan YY, O’Connor W, Rongvaux A, Van Rooijen N, Habermanh AM, Iwakura Y, Kuchroo VK, Kolls JK, Bluestone JA, Herold KC, Flavell RA (2011) Control of Th17 cells occurs in the small intestine. Nature 475:514-518.
  10. Gagliani N, Jofra T, Stabilini A, Valle A, Atkinson M, Roncarolo MG, Battaglia M (2010) Antigenspecific dependence of Tr1-cell therapy in preclinical models of islet transplantation. Diabetes 59:433439.

Our Team

Prof. Dr. Eva Tolosa

Insitute of Immunology

University Medical Center Hamburg-Eppendorf (UKE)

Prof. Phd Nicola Gagliani

I. Department of Medicine & Department of General, Visceral and Thoracic Surgery

University Medical Center Hamburg-Eppendorf (UKE)

M.Sc. Riekje Winzer

Insitute of Immunology

University Medical Center Hamburg-Eppendorf (UKE)

M.Sc. Filippo Cortesi

I. Department of Medicine & Department of General, Visceral and Thoracic Surgery

University Medical Center Hamburg-Eppendorf (UKE)

Nicola Scheibel

I. Department of Medicine & Department of General, Visceral and Thoracic Surgery

University Medical Center Hamburg-Eppendorf (UKE)

Contact

University Medical Center Hamburg-Eppendorf 
Department of Biochemistry and Molecular Cell Biology 
Martinistrasse 52
20246 Hamburg

Scientific Coordinator

Dr. Björn-Philipp Diercks
Fon: +49  (0) 40 7410 54338
E-Mail: b.diercks©uke.de

Administration

Laura Mitsching
Fon: +49  (0) 40 7410 50301
E-Mail: l.mitsching©uke.de