The biology of the immunoregulatory cytokines IFNγ, IL-18, and IL-22
H. Mühl (group leader), M. Bachmann (staff scientist), S. Gonther (PhD student), H. Stülb (PhD student), A. Ahmed (MD student), S. Rösser (Master student)
Most diseases accompanied with inflammation, autoimmunity, and infection are associated with changes in cytokine, chemokine, and growth factor production. We investigate roles of these mediators related to the processes of inflammation and carcinogenesis.
In particular, we study the biology of cytokines and mediators that are associated with Th1-like inflammation with focus on IFNγ, IL-22, the IL-1 family of cytokines, and nitric oxide.
Supported by DFG (DFG MU 1284/6-2)
und GRK 2336: AVE - Resolution of Inflammation
Selected Original Publications
Bachmann M, Pfeilschifter J, and Mühl H. Epigenetic regulation by CpG methylation splits strong from retarded IFNγ-induced IL-18BP in epithelial versus monocytic cells. BBA-GENE REGUL MECH, 1861(3): 191-199, 2018
Bachmann M, Pfeilschifter J, and Mühl H. A prominent role of IL-18 in acetaminophen-induced liver injury advocates its blockage for therapy of hepatic necroinflammation. Front Immunol, 9: 161. doi: 10.3389/fimmu.2018.00161. eCollection 2018
Chichelnitskiy E, Himmelseher B, Bachmann M, Pfeilschifter J, and Mühl H. Hypothermia promotes IL-22 expression and fine-tunes its biological activity. Front Immunol.8: 742, 2017
Scheiermann P, Bachmann M, Goren I, Zwissler B, Pfeilschifter J, and Mühl H. Application of interleukin-22 mediates protection in experimental acetaminophen-induced acute liver injury. Am J Pathol., 182(4):1107-13, 2013
Bachmann M, Ulziibat S, Härdle L, Pfeilschifter J, and Mühl H. IFNa converts IL-22 into a cytokine efficiently activating STAT1 and its downstream targets. Biochem Pharmacol., 85(3): 396-403, 2013
Kronenberger B, Rudloff I, Bachmann M, Brunner F, Kapper L, Filmann N, Waidmann O, Herrmann E, Pfeilschifter J, Zeuzem S, Piiper A, and Mühl H. Interleukin-22 predicts severity and death in advanced liver cirrhosis: A prospective cohort study.
BMC Medicine, 10 (1), 102, 2012
Bachmann M, Scheiermann P, Härdle L, Pfeilschifter J, and Mühl H. IL36γ/IL1F9 - an innate T-bet target in myeloid cells.
J Biol Chem., 287(50): 41684-96, 2012
Bachmann M, Horn K, Rudloff I, Goren I, Holdener M, Christen U, Darsow N, Hunfeld KP, Koehl U, Kind P, Pfeilschifter J, Kraiczy P, and Mühl H. Early production of IL-22 but not IL-17 by peripheral blood mononuclear cells exposed to live Borrelia burgdorferi: the role of monocytes and IL-1. PLoS Pathogens, 14;6(10):e1001144, 2010
Sadik CD, Bachmann M, Pfeilschifter J, and Mühl H. Activation of interferon regulatory factor-3 via Toll-like receptor 3 and immunomodulatory functions detected in A549 lung epithelial cells exposed to misplaced U1-snRNA. Nucleic Acids Res, 37(15):5041-56, 2009
Bachmann M, Paulukat J, Pfeilschifter J, and Mühl H. Molecular mechanisms of IL-18BP regulation in DLD-1 cells: pivotal direct action of the STAT1/GAS axis on the promoter level.
J Cell Mol Med, 2009, 13(8B), 1987-1994
Ziesché E, Bachmann M, Kleinert H, Pfeilschifter J, Mühl H. The IL-22/STAT3 pathway potentiates expression of iNOS in human colon carcinoma cells. J Biol Chem, 2007, 282(22), 16006-16015
Paulukat J, Bosmann M, Nold M, Garkisch S, Kämpfer H, Frank S, Raedle J, Zeuzem S, Pfeilschifter J, Mühl H. Expression and release of IL-18 binding protein in response to Interferon-g.
J Immunol 2001 Dec;167(12):7038-7043.
Mühl H, Bachmann M. IL-18/IL-18BP and IL-22/IL-22BP: Two interrelated couples with therapeutic potential. Cell Signal.. Aug 8:109388. doi: 10.1016/j.cellsig.2019.109388. [Epub ahead of print]., 2019
Mühl, H. STAT3, a key parameter of cytokine-driven tissue protection during sterile inflammation – the case of experimental acetaminophen (paracetamol)-induced liver damage. Front Immunol. 7: 163, 2016
Mühl H, Scheiermann P, Bachmann M, Härdle L, Heinrichs A, and Pfeilschifter J. IL-22 in tissue protective therapy. Br J Pharmacol, 169(4): 761-71. 2013
Mühl, H. Pro-Inflammatory Signaling by IL-10 and IL-22: Bad Habit Stirred up by Interferons? Front. Immunol, 2013; 4: 18, doi: 10.3389/fimmu.2013.00018
Mühl H, Bachmann M and Pfeilschifter J. Inducible NO synthase and antibacterial host defense in times of Th17/Th22/T22 immunity. Cell Microbiol, 13(3):340-8, 2011
Mühl H, Pfeilschifter J. Interleukin-18 bioactivity: a novel target for immunopharmacological anti-inflammatory intervention.
Eur J Pharmacol. 2004 Oct 1;500(1-3):63-71
Mühl H, Pfeilschifter J. Anti-inflammatory properties of pro-inflammatory interferon-gamma. Int Immunopharmacol. 2003 Sep;3(9):1247-55