A12

A12

Our project focusses on signalling by extracellular adenine nucleotides as a mechanism to regulate lymphocyte functions and inflammation in viral infections and other (chronic) inflammatory states. ATP released by cells in inflamed tissues can promote inflammation or be degraded by the ecto-nucleotidases CD39 and CD73 to adenosine, which reduces immune cell activation and dampens inflammation. We will examine how this is related to another major mechanism limiting inflammation, T cell exhaustion. Our goal is to explore the therapeutic potential of modulating extracellular adenine nucleotides to promote or dampen T cell function, inflammation and to drive T-cell differentiation.

Prof. Dr. Friedrich Haag

Selected publications (*equal contribution)

 

1. Wildner NH, Ahmadi P, Schulte S, Brauneck F, Kohsar M, Lütgehetmann M, Beisel C, Addo MM, Haag F, Schulze Zur Wiesch J (2021) B cell analysis in SARS-CoV-2 versus malaria: Increased frequencies of plasmablasts and atypical memory B cells in COVID-19. J Leukoc Biol 109: 77-90.
2. Libera J, Wittner M, Kantowski M, Woost R, Eberhard JM, de Heer J, Reher D, Huber S, Haag F, Schulze Zur Wiesch J. (2020) Decreased Frequency of Intestinal CD39(+) γδ(+) T Cells With Tissue-Resident Memory Phenotype in Inflammatory Bowel Disease. Front Immunol 11: 567472.
3. Ahmadi P, Hartjen P, Kohsar M, Kummer S, Schmiedel S, Bockmann JH, Fathi A, Huber S, Haag F, Schulze Zur Wiesch J. Defining the CD39/CD73 Axis in SARS-CoV-2 Infection: The CD73(-) Phenotype Identifies Polyfunctional Cytotoxic Lymphocytes. Cells 9(8):1750
4. Johnsen B, Kaschubowski KE, Nader S, Schneider E, Nicola JA, Fliegert R, Wolf IMA, Guse AH, Nikolaev VO, Koch-Nolte F, Haag F (2019) P2X7-mediated ATP secretion is accompanied by depletion of cytosolic ATP. Purinergic Signal 15: 155-166.
5. Danquah W, Meyer-Schwesinger C, Rissiek B, Pinto C, Serracant-Prat A, Amadi M, Iacenda D, Knop JH, Hammel A, Bergmann P, Schwarz N, Assunção J, Rotthier W, Haag F, Tolosa E, Bannas P, Boué-Grabot E, Magnus T, Laeremans T, Stortelers C, Koch-Nolte F (2016) Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation. Sci Transl Med 8: 366ra162.
6. Haag F, Buck F (2015) Identification and analysis of ADP-ribosylated proteins. Curr Top Microbiol Immunol 384: 33-50.
7. Hubert S, Rissiek B, Klages K, Huehn J, Sparwasser T, Haag F, Koch-Nolte F, Boyer O, Seman M, Adriouch S (2010) Extracellular NAD+ shapes the Foxp3+ regulatory T cell compartment through the ART2-P2X7 pathway. J Exp Med 207: 2561-2568.
8. Seman M, Adriouch S, Scheuplein F, Krebs C, Freese D, Glowacki G, Deterre P, Haag F, and Koch-Nolte F (2003). NAD-induced T cell death: ADP-ribosylation of cell surface proteins by ART2 activates the cytolytic P2X7 purinoceptor. Immunity 19: 571-582.
9. Adriouch S, Dox C, Welge V, Seman M, Koch-Nolte F, Haag F (2002) Cutting edge: a natural P451L mutation in the cytoplasmic domain impairs the function of the mouse P2X7 receptor. J Immunol 169: 4108-4112.

Prof. Dr. Julian Schulze zur Wiesch

Selected publications (*equal contribution)

 

1. 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, Schulze zur Wiesch J, 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. Sci Immunol 6(56):eabf6692.
2. Heide J., Schulte S., Kohsar M., Brehm T. T., Herrmann M., Karsten H., Marget M., Peine S., Johansson A. M., Sette A., Lütgehetmann M., Kwok W. W., *Sidney J., *Schulze Zur Wiesch J (2021) Broadly directed SARS-CoV-2-specific CD4+ T cell response includes frequently detected peptide specificities within the membrane and nucleoprotein in patients with acute and resolved COVID-19. PLoS Pathog 17(9):e1009842.
3. Brauneck F., Haag F., Woost R., Wildner N., Tolosa E., Rissiek A., Vohwinkel G., Wellbrock J., Bokemeyer C., Schulze Zur Wiesch J.*, Ackermann C.*, & Fiedler W*(2021) Increased frequency of TIGIT⁺CD73-CD8⁺ T cells with a TOX⁺ TCF-1low profile in patients with newly diagnosed and relapsed AML. Oncoimmunology10(1), 1930391.
4. Wildner NH, Ahmadi P, Schulte S, Brauneck, F, Kohsar M, Luetgehetmann M, Beisel C, Addo M, Haag F, Schulze zur Wiesch J (2021) B cell analysis in SARS-CoV-2 versus malaria: Increased frequencies of plasmablasts and atypical memory B cells in COVID-19. Journal of Leukocyte Biol 109: 77– 90.
5. Libera J, Wittner M, Kantowski M, Woost R, Eberhard JM, de Heer J, Reher D, Huber S, Haag F, Schulze Zur Wiesch J (2020) Decreased Frequency of Intestinal CD39+ gd+ T Cells With Tissue-Resident Memory Phenotype in Inflammatory Bowel Disease. Front Immunol 11:567472.
6. Herrmann M, Schulte S, Wildner NH, Wittner M, Brehm TT, Ramharter M, Woost R, Lohse AW, Jacobs T, Schulze Zur Wiesch J (2020) Analysis of Co-inhibitory Receptor Expression in COVID-19 Infection Compared to Acute Plasmodium falciparum Malaria: LAG-3 and TIM-3 Correlate With T Cell Activation and Course of Disease. Front Immunol 11:1870.
7. Eberhard JM, Angin M, Passaes C, Salgado M, Monceaux V, Knops E, Kobbe G, Jensen B, Christopeit M, Kröger N, Vandekerckhove L, Badiola J, Bandera A, Raj K, van Lunzen J, Hütter G, Kuball JHE, Martinez-Laperche C, Balsalobre P, Kwon M, Díez-Martín JL, Nijhuis M, Wensing A, Martinez-Picado J, Schulze Zur Wiesch J, Sáez-Cirión A (2020) Vulnerability to reservoir reseeding due to high immune activation after allogeneic hematopoietic stem cell transplantation in individuals with HIV-1. Sci Transl Med 12:eaay9355
8. Ackermann C, Smits M, Woost R, Eberhard JM, Peine S, Kummer S, Marget M, Kuntzen T, Kwok WW, Lohse AW, Jacobs T, Boettler T, Schulze Zur Wiesch J (2019) HCV-specific CD4+ T cells of patients with acute and chronic HCV infection display high expression of TIGIT and other co-inhibitory molecules. Sci Rep 9(1):10624.
9. Lindqvist M, van Lunzen J, Soghoian DZ, Kuhl BD, Ranasinghe S, Kranias G, Flanders MD, Cutler S, Yudanin N, Muller MI, Davis I, Farber D, Hartjen P, Haag F, Alter G, Schulze zur Wiesch J, Streeck H (2012) Expansion of HIV-specific T follicular helper cells in chronic HIV infection. J Clin Invest 122:3271-3280.
10. Schulze zur Wiesch J*, Ciuffreda D *, Lewis-Ximenez L, Kasprowicz V, Nolan B, Streeck H, Aneja J, Reyor L, Allen T, Lohse A, McGovern B, Chung R, Kwok W, Kim A, Lauer G (2012) Broadly directed virus-specific CD4+ T cell responses are primed during acute hepatitis C infection, but rapidly disappear from human blood with viral persistence. J Exp Med 209:6175.

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