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Bone marrow-derived CD169+ macrophages promote autoimmune hepatitis by recruiting CCR2+ monocytes via secreting CCL12
Open accessAbstract
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 Ly6C hi CD169 + 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.
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In ConA-induced autoimmune hepatitis, a bone marrow-derived CD169+ macrophage subset plays a pivotal role.
“Conversely, in immune-mediated injury like ConA-induced AIH, a bone marrow-derived CD169+ macrophage subset plays a pivotal role.”
From Macrophage duality in liver diseases: heterogeneity, plasticity, and the quest for precision therapeutics (2026) · cites this paper as [40]
In ConA-induced AIH, CD169+ macrophages activated by IFN-γ secrete CCL12 to recruit additional CCR2+ monocytes, establishing a feed-forward loop of inflammation.
“Activated by IFN-γ, these cells secrete CCL12 to recruit additional CCR2+ monocytes, establishing a feed-forward loop of inflammation (40).”
From Macrophage duality in liver diseases: heterogeneity, plasticity, and the quest for precision therapeutics (2026) · cites this paper as [40]
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Research works printed but not linked: 2
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- Chávez-Galán, L., Olleros, M. L., Vesin, D. & Garcia I. Much more than M1 and M2 macrophages, there are also CD169+ and TCR+ macrophages. Front. Immunol. 6, 263 (2015).
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Metadata
- Authors
- Lin, B., Zhang, H., Zhu, P., Chen, J., Li, D., Zhou, J., Zhang, T., Chen, Q., Tang, C., Song, X., Zeng, H., Wang, J., Zhang, J., You, Z., Ma, X., & Yu, C.
- Affiliations
- First Affiliated Hospital Zhejiang University (CN)
- Shanghai Jiao Tong University (CN)
- State Key Laboratory of Diagnosis and Treatment of Infectious Diseases (CN)
- Corresponding author
- You, Zhengrui
- Ma, Xiong
- Yu, Chaohui
- ORCID
- Venue
- Experimental & Molecular Medicine
- Published
- 2025-12-22
- Volume
- 57
- Issue
- 12
- Pages
- 2930-2942
- ISSN
- 1226-3613 (ISSN-L)
- 2092-6413
- PMC
- PMC12800274
- OpenAlex
- W7116741618
- Cited by
- 5
- References
- 35
- Citations by year
- 2026: 5
- FWCI
- 2.81
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Experimental & Molecular Medicine (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Natural Science Foundation of China (82030019, 82370573, 82270553, 82130017, 81830016, and 82330018)
- Natural Science Foundation of Zhejiang Province (LQ22H030011)
- Topics
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Keywords
- CD169+ macrophages, autoimmune hepatitis, CCL12, CCR2+ monocytes, interferon-gamma, bone marrow-derived macrophages, macrophage recruitment, liver inflammation, macrophage depletion, chemokine signaling, therapeutic target
- MeSH terms
- Animals, Disease Models, Animal, Female, Humans, Macrophages, Male, Mice, Inbred C57BL, Monocytes, Hepatitis, Autoimmune, Mice, Receptors, CCR2, Sialic Acid Binding Ig-like Lectin 1
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