# Bone marrow-derived CD169+ macrophages promote autoimmune hepatitis by recruiting CCR2+ monocytes via secreting CCL12

## TL;DR

CD169+ macrophages worsen autoimmune hepatitis by recruiting immune cells, suggesting they could be a new treatment target.

## Contribution

Identifies bone marrow-derived CD169+ macrophages as key drivers of autoimmune hepatitis via CCL12 secretion.

## Key findings

- CD169+ macrophages increase in autoimmune hepatitis and correlate with inflammation severity.
- Depleting CD169+ macrophages reduces liver damage and immune cell infiltration in mice.
- CCL12 neutralization improves autoimmune hepatitis outcomes.

## Abstract

CD169+ macrophages, a unique subset of macrophages that cannot be simply defined as M1 or M2 macrophages, have been reported to be associated with various autoimmune diseases. However, the role of CD169+ macrophages in autoimmune hepatitis (AIH) is largely unknown. Here we found that the infiltration of CD169+ macrophages increased in the liver of patients with AIH and strongly positively correlated with inflammation degree. In a mouse model, depletion of CD169+ macrophages ameliorated ConA-induced acute liver injury. Immune homeostasis was also improved when CD169+ macrophages were depleted, as the infiltration of monocytes, macrophages and T cells decreased. Bone marrow-derived Ly6ChiCD169+ macrophages were further identified as the crucial subset in AIH. Next, we found that CD169+ macrophages were IFNγ-responsive and IFNγ could induce the expression of CD169. In response to the IFNγ signal, CD169+ macrophages actively secrete chemokine (C–C motif) ligand (CCL12), thus recruiting CCR2+ monocytes and macrophages to exacerbate AIH. Finally, neutralizing CCL12 improved AIH. Our results suggest that bone marrow-derived CD169+ macrophages, the key subset of macrophages in AIH, actively secrete CCL12 in response to IFNγ to recruit CCR2+ monocytes and macrophages, thus exacerbating AIH. The CD169+ macrophages are a potential therapeutic target in AIH.

Autoimmune hepatitis (AIH) is a liver disease in which the immune system attacks liver cells. Researchers wanted to understand the role of a specific type of immune cell, CD169+ macrophages. The study involved analyzing liver tissues from 40 patients with AIH and conducting experiments on mice. They found that CD169+ macrophages increased in AIH and were linked to disease severity. In mice, removing these cells reduced liver damage. The study showed that bone marrow-derived CD169+ macrophages, not those from the liver itself, were crucial in worsening AIH. These cells produce a protein called CCL12, which attracts more immune cells to the liver. The researchers concluded that targeting these specific macrophages could be a new way to treat AIH. In the future, therapies could focus on reducing the activity of these cells to help manage or prevent AIH progression.

This summary was initially drafted using artificial intelligence, then revised and fact-checked by the author.