B2 - Induction and breaking of immune tolerance in the liver

B02_Herkel_Lohse_FP3

Principal Investigators:

Prof. Dr. rer. nat. Johannes Herkel
I. Department of Internal Medicine
University Medical Center Hamburg-Eppendorf
Martinistr. 52
20246 Hamburg
Germany
Phone: +49-40-7410-59736
Fax: +49-40-7410-58014
E-Mail: jherkel@uke.de

Prof. Dr. med. Ansgar W. Lohse
I. Department of Internal Medicine
University Medical Center Hamburg-Eppendorf
Martinistr. 52
20246 Hamburg
Germany
Phone: +49-40-7410-53910
Fax: +49-40-7410-58531
E-Mail: sekretariatlohse@uke.de

Participating staff:

Marko Hilken – MTA
Dr. Max Petri– PostDoc
Daria Krzikalla– PhD student

Project description

The liver has a distinct capacity to suppress inflammation and induce immune tolerance. However, the liver can be the target of autoimmune diseases in which the immune system attacks the liver. Thus far, it is not well understood why and how autoimmune diseases in this tolerogenic environment can occur.

We believe that the type of the antigen-presenting cell and the resulting CD4 T cell response are the major determinants that define whether the outcome is hepatic tolerance or autoimmune liver disease.

Here we study the functional consequences of autoreactive lymphocyte stimulation by different resident and infiltrating antigen presenting cells in the liver. We expect significant conceptual advance in understanding the elusive pathogenesis of autoimmune liver diseases facilitating the development of novel therapeutic approaches.

B2 in 60 SecondsVideoarchiv

online seit 21.11.2012

Our previous findings indicate that the generation of regulatory T cells (Tregs) by liver sinusoidal endothelial cells (LSECs) is a major mechanism of hepatic tolerance. We have developed a nanoparticle-based method for the selective delivery of autoantigen peptides to LSECs that enables antigen-specific Treg induction and effective treatment of autoimmune disease.

We currently investigate into the factors and mechanisms accounting for the extraordinary efficacy of our nanoparticle-based treatment technique. Moreover, we study immune decision making in the liver to identify the essential molecular switches that mediate the transition from hepatic tolerance to inflammation; such key molecules are potential therapeutic targets for the treatment of liver diseases.

Related news:

Lohse AW, Herkel J, Weiler-Normann C

Can Understanding the Pathogenesis of Autoimmune Hepatitis Lead to Rational Therapy?
Dig Dis. 2017;35(4):367-370. doi: 10.1159/000456588. Epub 2017 May 3.

Kozik JH, Trautmann T, Carambia A, Preti M, Lütgehetmann M, Krech T, Wiegard C, Heeren J, Herkel J

Attenuated viral hepatitis in Trem1-/- mice is associated with reduced inflammatory activity of neutrophils
Sci Rep. 2016 Jun 22;6:28556. doi: 10.1038/srep28556.

Carambia A, Freund B, Schwinge D, Bruns OT, Salmen SC, Ittrich H, Reimer R, Heine M, Huber S, Waurisch C, Eychmüller A, Wraith DC, Korn T, Nielsen P, Weller H, Schramm C, Lüth S, Lohse AW, Heeren J, Herkel J

Nanoparticle-based autoantigen delivery to Treg-inducing liver sinusoidal endothelial cells enables control of autoimmunity in mice
J Hepatol. 2015 Jun;62(6):1349-56. doi: 10.1016/j.jhep.2015.01.006. Epub 2015 Jan 21.

Herkel J.

Regulatory T Cells in Hepatic Immune Tolerance and Autoimmune Liver Diseases
Dig Dis. 2015;33 Suppl 2:70-4. doi: 10.1159/000440750. Epub 2015 Dec 7.