A14

A14 Project movie

A14

Project A14 focused on the role of CD73 as modulator of T cell responses. First, they found that activated human T cells shed CD73 from their cell membrane into extracellular vesicles (EVs), and these EVs are immune suppressive in a CD73-dependent manner. Second, in a mouse model of self-resolving intestinal inflammation, expression of CD73 on Th17 cells is crucial for restoring immune homeostasis. ADO, the metabolite generated by CD73, is a recognized immune suppressor. Project A14 disclosed that ADO receptor signaling on T cells suppresses their pro-inflammatory activity, but does not induce the production of anti-inflammatory cytokines (e.g. IL-10). Further work from project A14 identified TGF-b signaling as a fundamental mechanism for supporting the switch from a pro- to an anti-inflammatory T cell, i.e. immune adaptation, in the intestine, suggesting that only the coordinated action of TGF-β (for acquiring an anti-inflammatory phenotype) and ADO (for shutting down the pro-inflammatory function) guarantees T cell immune adaptation in the intestine. Interestingly, very recent data show that TGF-b signaling supports the expression of CD73 in intestinal Th17 cells.

Prof. Dr. Eva Tolosa

Selected publications (*equal contribution)

 

  1. Schneider E, Winzer R, Rissiek A, Ricklefs I, Meyer-Schwesinger C, Ricklefs FL, Bauche A, Behrends J, Reimer R, Brenna S, Wasielewski H, Lauten M, Rissiek B, Puig B, Cortesi F, Magnus T, Fliegert R, Müller CE, Gagliani N, Tolosa E (2021) CD73-mediated adenosine production by CD8 T cell-derived extracellular vesicles constitutes an intrinsic mechanism of immune suppression. Nat Commun 125911.
  2. Schneider E, Rissiek A, Winzer R, Puig B, Rissiek B, Haag F, Mittrücker HW, Magnus T, Tolosa E (2019) Generation and Function of Non-cell-bound CD73 in Inflammation. Front Immunol 10:1729
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. Brucklacher-Waldert V, Stuerner K, Kolster M, Wolthausen J, Tolosa E (2009) Phenotypical and functional characterization of T helper 17 cells in multiple sclerosis. Brain 132:3329-3341.
  9. 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.
  10. 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

Prof. Nicola Gagliani

Selected publications (*equal contribution)

 

  1. Zhao L, Giannou AD, Xu Y, Shiri AM, Liebold I, Steglich B, Bedke T, Zhang T, Lücke J, Scognamiglio P, Kempski J, Woestemeier A, Chen J, Agalioti T, Zazara DE, Lindner D, Janning M, Hennigs JK, Jagirdar RM, Kotsiou OS, Zarogiannis SG, Kobayashi Y, Izbicki JR, Ghosh S, Rothlin CV, Bosurgi L*, Huber S*, Gagliani N* (2021) Efferocytosis fuels malignant pleural effusion through TIMP1. Science Adv 7(33):eabd6734
  2. Poch T, Krause J, Casar C, Liwinski T, Glau L, Kaufmann M, Ahrenstorf AE, Hess LU, Ziegler AE, Martrus G, Lunemann S, Sebode M, Li J, Schwinge D, Krebs CF, Franke A, Friese MA, Oldhafer KJ, Fischer L, Altfeld M, Lohse AW, Huber S, Tolosa E, Gagliani N*, Schramm C* (2021) Single-cell atlas of hepatic T cells reveals expansion of liver-resident naive-like CD4+ T cells in primary sclerosing cholangitis. J Hepatol S0168-8278(21)00219-1.
  3. Zhao Y, Kilian C, Turner JE, Bosurgi L, Roedl K, Bartsch P, Gnirck AC, Cortesi F, Schultheiß C, Hellmig M, Enk LUB, Hausmann F, Borchers A, Wong MN, Paust HJ, Siracusa F, Scheibel N, Herrmann M, Rosati E, Bacher P, Kylies D, Jarczak D, Lütgehetmann M, Pfefferle S, Steurer S, Zur-Wiesch JS, Puelles VG, Sperhake JP, Addo MM, Lohse AW, Binder M, Huber S, Huber TB, Kluge S, Bonn S, Panzer U, Gagliani N*, Krebs CF* (2021) Clonal expansion and activation of tissue-resident memory-like Th17 cells expressing GM-CSF in the lungs of severe COVID-19 patients. Science Immunol 6(56):eabf6692.
  4. Xu H, Agalioti T, Zhao J, Steglich B, Wahib R, Vesely MCA, Bielecki P, Bailis W, Jackson R, Perez D, Izbicki J, Licona-Limón P, Kaartinen V, Geginat J, Esplugues E, Tolosa E, Huber S, Flavell RA, Gagliani N (2020) The induction and function of the anti-inflammatory fate of TH17 cells. Nat Commun 11:3334
  5. Kempski J, Giannou AD, Riecken K, Zhao L, Steglich B, Lücke J, Garcia-Perez L, Karstens KF, Wöstemeier A, Nawrocki M, Pelczar P, Witkowski M, Nilsson S, Konczalla L, Shiri AM, Kempska J, Wahib R, Brockmann L, Huber P, Gnirck AC, Turner JE, Zazara DE, Arck PC, Stein A, Simon R, Daubmann A, Meiners J, Perez D, Strowig T, Koni P, Kruglov AA, Sauter G, Izbicki JR, Guse AH, Rösch T, Lohse AW, Flavell RA, Gagliani N*, Huber S.* IL22BP Mediates the Antitumor Effects of Lymphotoxin Against Colorectal Tumors in Mice and Humans. Gastroenterology 159(4):1417-1430.e3.
  6. Amezcua Vesely MC, Pallis P, Bielecki P, Low JS, Zhao J, Harman CCD, Kroehling L, Jackson R, Bailis W, Licona-Limón P, Xu H, Iijima N, Pillai PS, Kaplan DH, Weaver CT, Kluger Y, Kowalczyk MS, Iwasaki A, Pereira JP, Esplugues E, Gagliani N*, Flavell RA* (2019) Effector TH17 Cells Give Rise to Long-Lived TRM Cells that Are Essential for an Immediate Response against Bacterial Infection. Cell 178(5):1176-1188.e15.
  7. Brockmann L, Soukou S, Steglich B, Czarnewski P, Zhao L, Wende S, Bedke T, Ergen C, Manthey C, Agalioti T, Geffken M, Seiz O, Parigi SM, Sorini C, Geginat J, Fujio K, Jacobs T, Roesch T, Izbicki JR, Lohse AW, Flavell RA, Krebs C, Gustafsson JA, Antonson P, Roncarolo MG, Villablanca EJ, Gagliani N*, Huber S.* Molecular and functional heterogeneity of IL-10-producing CD4+ T cells. Nature Commun 9(1):5457.
  8. 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.
  9. Gagliani N, Vesely MC, Iseppon A, Brockmann L, Xu H, Palm NW, de Zoete MR, Licona-Limon P, Paiva RS, Ching T, Weaver C, Zi X, Pan X, Fan R, Garmire LX, Cotton M J, Drier Y, Bernstein B, Geginat J, Stockinger B, Esplugues E, Huber S*, Flavell RA* (2015) Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation. Nature 523:221-225.
  10. Gagliani N*, Magnani CF*, Huber S*, Gianolini ME, Pala M, Licona-Limon P, Guo B, Herbert DR, Bulfone A, Trentini F, Di Serio C, Bacchetta R, Andreani M, Brockmann L, Gregori S, Flavell RA, Roncarolo MG (2013) Coexpression of CD49b and LAG-3 identifies human and mouse T regulatory type 1 cells. Nature Med 19(6):739-46

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)

Dr. Enja Schneider

Insitute of Immunology

University Medical Center Hamburg-Eppendorf (UKE)

 

 

Dr. Filippo Cortesi

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)

 

 

Friederike Lay

Insitute of Immunology

University Medical Center Hamburg-Eppendorf (UKE)

 

 

Hanna Lorenz

Insitute of Immunology

University Medical Center Hamburg-Eppendorf (UKE)

 

 

Niklas Eich

Insitute of Immunology

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