A14

A14

The ability of effector T helper cells to switch from a pro- to an anti-inflammatory function, i.e. immune adaptation, is fundamental for intestinal homeostasis. We hypothesize that immune adaptation in the intestine is controlled by the availability of ATP and adenosine (ADO) in the intestinal environment. In this second period we will address (i) the consequences of ATP sensing by intestinal Th17 cells, (ii) the role of cell- and extracellular vesicle-associated purinergic enzymes in the ATP to ADO degradation in the intestine, (iii) the consequences of the loss of adenosine A2A receptor signaling in Th17 cells, and (iv) the molecular mechanisms regulating the expression of CD73 and A2A receptors in 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 12, 5911.
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 T_H17 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 T_H17 Cells Give Rise to Long-Lived T_RM 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