For a May explainer, weâ€™d like to spotlight liver fibrosis. Two recent papers from Emory research teams in the journal Hepatology focus on this process.
Liver fibrosis is an accumulation of scar tissue and proteins outside cells that occurs as a result of chronic damage to the liver. It involves inflammation and immune cells, as well as activation of a type of cell in the liver (hepatic stellate cells), which usually stores fat and vitamin A.Â Fibrosis and cirrhosis are not the same. Think of it this way: cirrhosis is the late stage of the disease, but fibrosis is how someone can get there.
One of the Hepatology papers comes at liver fibrosis from a malaria angle. Patrice Mimche, Tracey Lamb and colleagues show the involvement of EphB2 tyrosine kinase, a signaling molecule not previously known to be involved in liver fibrosis.
Malaria parasites have a complex life cycle, growing in the liver and then in the blood. Lamb says an important part of her paper was the finding that in mouse malaria infection, EphB2 is activated during the blood stageÂ on immune cells infiltrating intoÂ the liver. EphB2 (an active drug discovery target)Â may be acting as a tissue-specific adhesion molecule, she says.
In their paper, the researchers show mice lacking EphB2 are protected from malaria-induced liver fibrosis despite having parasites in the liver, they report. Mice lacking EphB2 also develop less liver fibrosis in a non-malarial toxin (carbon tetrachloride)-mediated model. EphB2 has been studied more for its roles in cell migration, neuronal development and cancer.
A second paper, from postdoc Manoj Thapa, hepatitis C specialist Arash Grakoui and colleagues, looks at the involvement of B cells in liver fibrosis. Although B cellsâ€™ main functions generallyÂ revolve aroundÂ antibody production, here theyâ€™re doing something different, involving innate immunity and inflammation. In the carbon tetrachloride model of liver fibrosis, mice lacking B cells do not develop liver fibrosis.
“Our study highlights an important pathogenic role for liver B cells that was previously unknown. We highlight the liver B cell as an important innate component of the liver immune microenvironment with significant potential as a therapeutic target,” the authors conclude.