Myeloid-Derived Suppressive Cells Deficient in Liver X Receptor α Protected From Autoimmune Hepatitis

Li, Bo; Lian, Min; Li, Yikang; Qian, Qiwei; Zhang, Jun; Liu, Qiaoyan; Ma, Xiong

doi:10.3389/fimmu.2021.732102

Cited by 8 publications

(9 citation statements)

References 46 publications

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“…It has been shown that loss of LXRα/β disrupted the balance of hematopoietic population and increased BM and PB myeloid cell numbers (Rasheed et al., 2018). Others have also shown that loss of LXRα resulted in an increased accumulation of myeloid‐derived suppressor cells (MDSCs) in liver (Li, Lian, et al., 2021), and that activation of LXR decreased MDSC abundance in animal models and in individuals treated in a clinical trial (Tavazoie et al., 2018). We have shown previously a great overlap of MDSCs and OCPs and the osteoclastogenic potential of MDSCs (Cai et al., 2020; Li, Zhao, et al., 2021; Su et al., 2017).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, we have recently shown that chronic Pg infection significantly downregulates the gene expression of ApoE, a transcriptional target of LXRs, in OCPs (Zhao et al., 2020). In addition, others have shown that LXRs are important for maintaining the balance of hematopoietic populations (Rasheed et al., 2018) and the abrogation of LXRs increases the number of myeloid progenitor populations (Li, Lian, et al., 2021). These data suggest that LXRs are involved in the modulation of OCPs.…”

Section: Introductionmentioning

confidence: 99%

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Activation of liver X receptors suppresses the abundance and osteoclastogenic potential of osteoclast precursors and periodontal bone loss

Zhao,

Yang,

Ferreira

et al. 2023

Molecular Oral Microbiology

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Liver‐X receptors (LXRs) are essential nuclear hormone receptors involved in cholesterol and lipid metabolism. They are also believed to regulate inflammation and physiological and pathological bone turnover. We have previously shown that infection with the periodontal pathogen Porphyromonas gingivalis (Pg) in mice increases the abundance of CD11b+c‐fms+Ly6Chi cells in bone marrow (BM), spleen (SPL), and peripheral blood. These cells also demonstrated enhanced osteoclastogenic activity and a distinctive gene profile following Pg infection. Here, we investigated the role of LXRs in regulating these osteoclast precursors (OCPs) and periodontal bone loss. We found that Pg infection downregulates the gene expression of LXRs, as well as ApoE, a transcription target of LXRs, in CD11b+c‐fms+Ly6Chi OCPs. Activation of LXRs by treatment with GW3965, a selective LXR agonist, significantly decreased Pg‐induced accumulation of CD11b+c‐fms+Ly6Chi population in BM and SPL. GW3965 treatment also significantly suppressed the osteoclastogenic potential of these OCPs induced by Pg infection. Furthermore, the activation of LXRs reduces the abundance of OCPs systemically in BM and locally in the periodontium, as well as mitigates gingival c‐fms expression and periodontal bone loss in a ligature‐induced periodontitis model. These data implicate a novel role of LXRs in regulating OCP abundance and osteoclastogenic potential in inflammatory bone loss.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Activation of liver X receptors suppresses the abundance and osteoclastogenic potential of osteoclast precursors and periodontal bone loss

Zhao,

Yang,

Ferreira

et al. 2023

Molecular Oral Microbiology

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“…Elimination of LXRα promotes amplification of MDSCs by downregulating IRF-8 to significantly ameliorate hepatic immune injury. 59 Deletion of RIP3 showed similar protective effects. RIP3 inhibition led to an increase in CD11b+Gr1+ MDSCs with immunomodulatory properties in the liver, spleen and peripheral blood.…”

Section: Mdscs and Autoimmune Liver Diseasementioning

confidence: 76%

“…Liver X receptors (lxRs), key nuclear receptors linking lipid metabolism and immune responses are upregulated in patients with AIH and co‐localize with hepatic MDSCs. Elimination of LXRα promotes amplification of MDSCs by downregulating IRF‐8 to significantly ameliorate hepatic immune injury 59 . Deletion of RIP3 showed similar protective effects.…”

Section: Current Status Of Research On Mdscs In Liver Diseasementioning

confidence: 93%

Progress in research on the role played by myeloid‐derived suppressor cells in liver diseases

et al. 2023

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Myeloid‐derived suppressor cells (MDSCs) refer to a group of immature myeloid cells with potent immunosuppressive capacity upon activation by pathological conditions. Because of their potent immunosuppressive ability, MDSCs have garnered extensive attention in the past few years in the fields of oncology, infection, chronic inflammation and autoimmune diseases. Research on MDSCs in liver diseases has gradually increased, and their potential therapeutic roles will be further explored. This review presents a summary of the involvement and the role played by MDSCs in liver diseases, thus identifying their potential targets for the treatment of liver diseases and providing new directions for liver disease‐related research.

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“…In addition to macrophages, NKT, NK, T cells, and myeloid-derived suppressor cells play important roles in acute liver injury. [39][40][41] Hence, the proportions of NKT (CD3 + NK1.1 + ), NK (CD3 − NK1.1 + ), T (CD3 + NK1.1 − ), and myeloid-derived suppressor cells (MDSCs, CD11b + Gr-1 + ) cells in the liver were measured using flow cytometry (detailed flow gate strategies are shown in Figure S8). The percentage of activated NKT, NK, and T cells increased following the Con A injection.…”

Section: Il-28a Deficiency Regulated M1 Macrophage Activation In Con ...mentioning

confidence: 99%

Interleukin 28A aggravates Con A‐induced acute liver injury by promoting the recruitment of M1 macrophages

Zhang,

Cheng,

Zhang

et al. 2024

The FASEB Journal

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Immune‐mediated acute hepatic injury is characterized by the destruction of a large number of hepatocytes and severe liver function damage. Interleukin‐28A (IL‐28A), a member of the IL‐10 family, is notable for its antiviral properties. However, despite advances in our understanding of IL‐28A, its role in immune‐mediated acute injury remains unclear. The present study investigated the role of IL‐28A in concanavalin A (Con A)‐induced acute immune liver injury. After Con A injection in mice, IL‐28A level significantly increased. IL‐28A deficiency was found to protect mice from acute liver injury, prolong survival time, and reduce serum aspartate aminotransferase and alanine aminotransferase levels. In contrast, recombinant IL‐28A aggravated liver injury in mice. The proportion of activated M1 macrophages was significantly lower in the IL‐28A‐deficiency group than in the wild‐type mouse group. In adoptive transfer experiments, M1 macrophages from WT could exacerbate mice acute liver injury symptoms in the IL‐28A deficiency group. Furthermore, the expression of proinflammatory cytokines, including tumor necrosis factor‐α (TNF‐α), IL‐12, IL‐6, and IL‐1β, by M1 macrophages decreased significantly in the IL‐28A‐deficiency group. Western blotting demonstrated that IL‐28A deficiency could limit M1 macrophage polarization by modulating the nuclear factor (NF)‐κB, mitogen‐activated protein kinase (MAPK), and interferon regulatory factor (IRF) signaling pathways. In summary, IL‐28A deletion plays an important protective role in the Con A‐induced acute liver injury model and IL‐28A deficiency inhibits the activation of M1 macrophages by inhibiting the NF‐κB, MAPK, and IRF signaling pathways. These results provide a potential new target for the treatment of immune‐related hepatic injury.

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Myeloid-Derived Suppressive Cells Deficient in Liver X Receptor α Protected From Autoimmune Hepatitis

Cited by 8 publications

References 46 publications

Activation of liver X receptors suppresses the abundance and osteoclastogenic potential of osteoclast precursors and periodontal bone loss

Activation of liver X receptors suppresses the abundance and osteoclastogenic potential of osteoclast precursors and periodontal bone loss

Progress in research on the role played by myeloid‐derived suppressor cells in liver diseases

Interleukin 28A aggravates Con A‐induced acute liver injury by promoting the recruitment of M1 macrophages

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