P4 Progression from NAFLD to NASH: Miscommunication between the intestinal microbiota and CD4 T cells as a potential cause

P04_Gagliani_FP3

Principal Investigator:
Prof. Nicoala Gagliani, Ph.D.
I. Medical Center
General, Visceral and Thoracic Surgery Department
University Medical Center Hamburg-Eppendorf
Martinistrasse 52
20246 Hamburg
Tel.: +49-40-7410-52495
Fax: +49-40-7410-59092
E-Mail: n.gagliani@uke.de

Participating staff:

Dr. med. Scognamiglio -PostDoc
Dr. Babette Steglich – PostDoc
Merket – TA

Project Description

The reason why only a fraction of patients suffering from Non Alcoholic Fatty Liver Disease (NAFLD) progress to Non-Alcoholic Steatohepatitis (NASH) is not clear. Studies on mouse models suggest a role of the intestinal microbiota in this progression.

The intestinal microbiota has an active crosstalk with the immune system, in particular with the CD4+ T cells. CD4+ T cells are considered the main orchestrator of the immune response and they exert their function by secreting a variety of cytokines. Based on this, we hypothesise that “bad” intestinal microbiota promotes the capacity of intestine-derived CD4+ T cells to co-produce multiple cytokines: a cellular phenomenon described as plasticity. In the liver, these plastic cells orchestrate a pathogenic immune response driving NASH.

In summary, this project aims to establish a connection among the intestinal microbiota, the immune system and NASH development and in doing so, identify new therapeutic targets for futures therapies.