News Detail

11.08.2021

Developing hematopoietic stem cells in adult liver – Envisaging a liver-lung axis?

ILBD/CPC’s Tom Conlon and Ali Önder Yildirim together with Percy Knolle (TUM) provided their expert-view in a Research Highlight on exciting work by Bai et al. (University of Science and Technology of China, Hefei) - published in Signal Transduction and Targeted Therapy.

Immune cell influx and lung damage – characteristic features of COPD - © Helmholtz Zentrum München

The researchers around Lu Bai identified interferon-gamma (IFN-γ) secreted by type 1 innate lymphoid cells (ILC1s) self-perpetuated their own sustained local development from resident hematopoietic stem cells (HSCs) in adult liver, that were originally derived from the fetal liver.

In their Research Highlight, Conlon and Yildirim confirm that this leads to an interesting hypothesis: IFN-γ production by type 1 innate lymphoid cells (ILC1s) during acute liver injury not only promotes hepatocyte survival. It also leads to the self-perpetuating development of further ILC1s to counteract the ongoing injury. This is contributing a lot to our understanding of extramedullary hematopoiesis.

According to Conlon and Yildirim this leads to another hypothesis concerning the lung:

It is known that IFN-γ levels are increased in many chronic diseases like during COPD pathogenesis. They are accompanied by increased numbers of circulating ILC1s which correlates with disease severity and exacerbation episodes. If IFN-γ regulates the generation of resident immune cells in various other organs: Can we therefore envisage a “liver-lung axis” where ILC1s generated in the liver from liver resident LSM progenitor cells in response to increased IFN-γ levels contributes to lung pathology?

This needs to be confirmed experimentally, but offers an exciting vision for the future where targeted therapy against the auto-enhancement of ILC1 generation may open novel therapeutic avenues in the fight against lung damage resulting from chronic respiratory conditions such as COPD.

Conlon/Yildirim article „Local tissue development of type 1 innate lymphoid cells: guided by interferon-gamma“, Sig Transduct Target Ther, 2021

Underlying publication from Bai, L. et al. „Liver type 1 innate lymphoid cells develop locally via an interferon-gamma-dependent loop“, Science, 2021