Identified a new subset of liver cells: they could be effective against hepatitis B

A San Raffaele study has identified a new subset of immune system cell with antiviral activity. They are called Kupffer 2 (KC2) cells, hitherto unknown, and appear to improve the ability to fight infections. This discovery adds an important piece to the complex network of immune responses to viral infections and may have important therapeutic implications for hepatitis B.

Kupffer cells reside in the liver, where they play the dual role of first defense against infections and blood “scavengers” by removing damaged or aged cells. The San Raffaele researchers have discovered a second class of cells, called type 2 Kupffer cells, which mediate the activation of the immune system.

It is precisely in the liver that the team directed by Matteo Iannacone, Associate Professor of General Pathology at the Vita-Salute San Raffaele University, concentrates a part of its research activity, trying to reveal how the immune system is able to orchestrate its activity against pathogens and tumors.

Already in 2019, Prof. Iannacone's team had published a study in the prestigious journal Nature in which they described the role of interleukin-2 (IL-2), a molecule-messenger of immunity, in the activation of a specific class of white blood cells, CD8+ T lymphocytes against hepatitis B virus (HBV). Today, thanks to a mouse model, researchers from the Dynamics of Immune Responses Unit have taken an extra step by discovering that type 2 Kupffer cells mediate the activation of lymphocytes.

The discovery, published in the latest issue of Immunity, identified peculiar characteristics of Kupffer 2 cells, which differentiate them from "conventional" ones. Thanks to the use of sophisticated RNA sequencing and cytometry techniques for the analysis of cell receptors, the researchers have in fact discovered the Kupffer 2 cells, once stimulated by interleukin-2, are able to expose on their surface fragments of the hepatitis B virus to trigger the lymphocyte response (a mechanism known as antigen cross-presentation).

On the contrary, we know that “conventional” Kupffer cells are not efficient in this process: chronic viral hepatitis could also be due to this inefficiency. So far the study has been carried out in the liver of an animal model, however, cells with genetic characteristics similar to murine Kupffer 2 cells have recently also been identified in humans. If these cells had the same peculiarities described in the mouse, it would be possible to hypothesize to stimulate them, for example through interleukin-2, as a therapy for chronic forms of hepatitis B.