TREM2 sustains macrophage-hepatocyte metabolic coordination in nonalcoholic fatty liver disease and sepsis

Hou, Jinchao; Zhang, Jue; Cui, Ping; Zhou, Yingyue; Liu, Can; Wu, Xiaoliang; Ji, Yun; Wang, Sicong; Cheng, Baoli; Ye, Hui; Shu, Liqi; Zhang, Kai; Wang, Di; Xu, Jielin; Shu, Qiang; Colonna, Marco; Fang, Xiangming

doi:10.1172/jci135197

Cited by 144 publications

(120 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Strikingly, these TREM-2+ scar-associated macrophages share many similarities with “lipid-associated macrophages” in inflamed adipose tissue in obesity models, in which these cells controlled adipose tissue characteristics [ 104 ]. Further evidence suggests that TREM-2 actually has a regulatory role in various rodent liver injury models [ 105 , 106 ]. However, these TREM-2 positive macrophages could be a heterogeneous subset with opposing functions depending on the context of liver injury.…”

Section: Chronic Liver Injurymentioning

confidence: 99%

Liver Injury and the Macrophage Issue: Molecular and Mechanistic Facts and Their Clinical Relevance

Roohani

Tacke

2021

IJMS

View full text Add to dashboard Cite

The liver is an essential immunological organ due to its gatekeeper position to bypassing antigens from the intestinal blood flow and microbial products from the intestinal commensals. The tissue-resident liver macrophages, termed Kupffer cells, represent key phagocytes that closely interact with local parenchymal, interstitial and other immunological cells in the liver to maintain homeostasis and tolerance against harmless antigens. Upon liver injury, the pool of hepatic macrophages expands dramatically by infiltrating bone marrow-/monocyte-derived macrophages. The interplay of the injured microenvironment and altered macrophage pool skews the subsequent course of liver injuries. It may range from complete recovery to chronic inflammation, fibrosis, cirrhosis and eventually hepatocellular cancer. This review summarizes current knowledge on the classification and role of hepatic macrophages in the healthy and injured liver.

show abstract

Section: Chronic Liver Injurymentioning

confidence: 99%

Liver Injury and the Macrophage Issue: Molecular and Mechanistic Facts and Their Clinical Relevance

Roohani

Tacke

2021

IJMS

View full text Add to dashboard Cite

show abstract

“…( 13 ) In addition, a remarkable subset of macrophages expressing the lipid receptor, triggering receptor expressed on myeloid cells 2, that expands in the NASH liver to coordinate hepatocyte energy supply and mitochondrial function, has been identified. ( 14 ) The liver contains a reservoir of classical (cDCs) and plasmacytoid (pDCs) dendritic cells (DCs) strategically located in the subcapsular space, between hepatocytes, and in the vasculature. ( 15 ) In human NASH, the ratio of cDC subsets shifts toward increased type 2 cDCs that could activate pathogenic T cells.…”

Section: The Nafld Inflammatory Environment At a Glancementioning

confidence: 99%

The Emerging Role of B Cells in the Pathogenesis of NAFLD

et al. 2021

View full text Add to dashboard Cite

NAFLD is one of the leading causes of abnormal liver function worldwide. NAFLD refers to a group of liver conditions ranging from nonalcoholic fatty liver to NASH, which involves inflammation, hepatocellular damage, and fibrosis. Triggering of inflammation in NASH is a key event in the progression of the disease, and identifying the factors that initiate or dysregulate this process is needed to develop strategies for its prevention or treatment. B cells have been implicated in several autoimmune and inflammatory diseases. However, their role in the pathogenesis of NAFLD and NASH is less clear. This review discusses the emerging evidence implicating intrahepatic B cells in the progression of NAFLD. We highlight the potential mechanisms of B-cell activation during NAFLD, such as increased hepatic expression of B-cell-activating factor, augmented oxidative stress, and translocation of gut-derived microbial products. We discuss the possible effector functions by which B cells promote NAFLD, including the production of proinflammatory cytokines and regulation of intrahepatic T cells and macrophages. Finally, we highlight the role of regulatory and IgA + B cells in the pathogenesis of NASH-associated HCC. In this review, we make the case that future research is needed to investigate the potential of B-cell-targeting strategies for the treatment of NAFLD. (Hepatology 2021;0:1-10). The NAFLD Inflammatory Environment at a Glance Role oF INNate IMMUNe CellSThe liver receives a constant influx of gut-derived products and acts as a firewall for the antigen-rich

show abstract

“…31 In cirrhotic patients and a mouse model of non-alcoholic fatty liver disease, TREM2 is highly expressed in liver CD9 + macrophages, which resemble lipid-associated macrophages and protect hepatocytes from lipid accumulation. [32][33][34] In atherosclerosis, TREM2 contributes to lipid catabolism in macrophages of atherosclerotic plaques. 35 The expression of TREM2 has been recently reported in TAMs of cancer patients and mouse tumor models, 36,37 and two studies showed that TREM2 sustains immunosuppressive TAMs.…”

Section: Trem2mentioning

confidence: 99%

Turning enemies into allies—reprogramming tumor-associated macrophages for cancer therapy

Molgora

Colonna

2021

Med

Self Cite

View full text Add to dashboard Cite

Checkpoint blockade therapies that target inhibitory receptors on T cells have revolutionized clinical oncology. Antibodies targeting CTLA-4 or the PD-1/PD-1 ligand (PD-L1) axis are now successfully used alone or in combination with chemotherapy for numerous tumor types. Despite the clinical success of checkpoint blockade therapies, tumors exploit multiple mechanisms to escape or subvert the anti-tumor T cell response. Within the tumor microenvironment, tumor-associated macrophages (TAMs) can suppress T cell responses and facilitate tumor growth in various ways, ultimately debilitating clinical responses to T cell checkpoint inhibitors. There is therefore significant interest in identifying biologicals and drugs that target immunosuppressive TAM within the tumor microenvironment and can be combined with immune checkpoint inhibitors. Here, we review approaches that are currently being evaluated to convert immunosuppressive TAM into immunostimulatory macrophages that promote T cell responses and tumor elimination.

show abstract

TREM2 sustains macrophage-hepatocyte metabolic coordination in nonalcoholic fatty liver disease and sepsis

Cited by 144 publications

References 52 publications

Liver Injury and the Macrophage Issue: Molecular and Mechanistic Facts and Their Clinical Relevance

Liver Injury and the Macrophage Issue: Molecular and Mechanistic Facts and Their Clinical Relevance

The Emerging Role of B Cells in the Pathogenesis of NAFLD

Turning enemies into allies—reprogramming tumor-associated macrophages for cancer therapy

Contact Info

Product

Resources

About