A03

A03: Summary

Several adenine nucleotides (AN) have been identified as Ca2+ mobilizing 2nd messengers in immune cells. CD38 is, at least in part, responsible for their formation and interconversion, and initial results suggest a role of CD38 in systemic and intestinal inflammation. The aim of the project is to unravel the role of AN in T cell function. Therefore, we will investigate T cells deficient in different AN-activated Ca2+ channels in vitro and in vivo in mouse models for intestinal inflammation. We expect that our study will clarify the function of distinct AN and their target ion channels in T cell differentiation and function particularly in the intestine.

Prof. Dr. Samuel Huber

Selected publications

 

  1. 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 (2020) IL22BP Mediates the Antitumor Effects of Lymphotoxin Against Colorectal Tumors in Mice and Humans. Gastroenterology 2020 Oct;159(4):1417-1430.e3
  2. Perez LG, Kempski J, McGee HM, Pelzcar P, Agalioti T, Giannou A, Konczalla L, Brockmann L, Wahib R, Xu H, Vesely MCA, Soukou S, Steglich B, Bedke T, Manthey C, Seiz O, Diercks BP, Gnafakis S, Guse AH, Perez D, Izbicki JR, Gagliani N, Flavell RA, Huber S (2020) TGF-β signaling in Th17 cells promotes IL-22 production and colitis-associated colon cancer. Nat Commun 2020 May 25;11(1):2608
  3. 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.
  4. Pelczar P, Witkowski M, Perez LG, Kempski J, Hammel AG, Brockmann L, Kleinschmidt D, Wende S, Haueis C, Bedke T, Witkowski M, Krasemann S, Steurer S, Booth CJ, Busch P, Konig A, Rauch U, Benten D, Izbicki JR, Rosch 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 354:358-362.
  5. 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.
  6. 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. Nat Med 19:739-746.
  7. Hu B, Elinav E, Huber S, Strowig T, Hao L, Hafemann A, Jin C, Eisenbarth SC, Flavell RA (2013) Microbiota-induced activation of epithelial IL-6 signaling links inflammasome-driven inflammation with transmissible cancer. PNAS 110:9862-9867.
  8. Huber S*, Gagliani N*, Zenewicz LA, Huber FJ, Bosurgi L, Hu B, Hedl M, Zhang W, O’Connor W, Murphy AJ, 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.
  9. Esplugues E*, Huber S *, Gagliani N, Hauser AE, Town T, Wan YY, O'Connor WJr, Rongvaux A, Van Rooijen N, Haberman 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. Huber S *, Gagliani N*, Esplugues E*, O'Connor WJr, Huber FJ, Chaudhry A, Kamanaka M, Kobayashi Y, Booth CJ, Rudensky AY, Roncarolo MG, 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-10-dependent manner. Immunity 34: 554-565.

 

 

 

 

Prof. Dr. Hans-Willi Mittrücker

Selected publications

 

  1. 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 2019 Jul 26;10:1729
  2. Mahnke J, Schumacher V, Ahrens S, Käding N, Feldhoff LM, Huber M, Rupp J, Raczkowski F, Mittrücker HW (2016) Interferon Regulatory Factor 4 controls TH1 cell effector function and metabolism. Sci Rep 6:35521.
  3. Yan I, Schwarz J, Lücke K, Schumacher N, Schumacher V, Schmidt S, Rabe B, Saftig P, Donners M, Rose-John S, Mittrücker HW*, Chalaris A* (2016) ADAM17 controls IL-6 signaling by cleavage of the murine IL-6Rα from the cell surface of leukocytes during inflammatory responses. J Leukoc Biol 99:749-760. *equal contribution as last authors
  4. Hünemörder S, Treder J, Ahrens S, Schumacher V, Paust HJ, Menter T, Matthys P, Kamradt T, Meyer-Schwesinger C, Panzer U, Hopfer H, Mittrücker HW (2015) TH1 and TH17 cells promote crescent formation in experimental autoimmune glomerulonephritis. J Pathol 237:62-71.
  5. Raczkowski F, Ritter J, Heesch K, Schumacher V, Guralnik A, Höcker L, Raifer H, Klein M, Bopp T, Harb H, Kesper DA, Pfefferle PI, Grusdat M, Lang PA, Mittrücker HW*, Huber M* (2013) The transcription factor Interferon Regulatory Factor 4 is required for the generation of protective effector CD8+ T cells. Proc Natl Acad Sci USA 110:15019-15124. *equal contribution as last authors
  6. Hoge J, Yan I, Jänner N, Schumacher V, Chalaris A, Steinmetz OM, Engel DR, Scheller J, RoseJohn S, Mittrücker HW (2013) IL-6 controls the innate immune response against Listeria monocytogenes via classical IL-6 signaling. J Immunol 190:703-711.
  7. Mittrücker HW, Steinhoff U, Köhler A, Krause M, Lazar D, Mex P, Miekley D, Kaufmann SHE (2007) Poor correlation between BCG vaccination-induced T cell responses and protection against tuberculosis. Proc Natl Acad Sci USA 104:12434-12439.
  8. Kursar M, Höpken UE, Koch M, Köhler A, Lipp M, Kaufmann SHE, Mittrücker HW (2005) Differential requirements for the chemokine receptor CCR7 in T-cell activation during Listeria monocytogenes infection. J Exp Med 201:1447-1457.
  9. Kursar M, Bonhagen K, Fensterle J, Köhler A, Hurwitz R, Kamradt T, Kaufmann SHE, Mittrücker HW (2002) Regulatory CD4+ CD25+ T cells restrict memory CD8+ T cell responses. J Exp Med 196:15851592.
  10. Mittrücker HW, Matsuyama T, Grossman A, Kündig TM, Potter J, Shahinian A, Wakeham A, Patterson B, Ohashi PS, Mak TW (1997) Requirement for the transcription factor LSIRF/IRF4 for mature B and T lymphocyte function. Science. 275:540-543.

Our Team

Prof. Dr. Samuel Huber

I. Medical Clinic and Polyclinic

University Medical Centre Hamburg-Eppendorf (UKE)

Prof. Dr. Hans-Willi Mittrücker

Insitute of Immunology

University Medical Centre Hamburg-Eppendorf (UKE)

Dr. Mikolaj Nawrocki

I. Medical Clinic and Polyclinic

University Medical Centre Hamburg-Eppendorf (UKE)

M.Sc. Niels Lory

 
Insitute of Immunology

University Medical Centre 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