IL-34 Inhibits Acute Rejection of Rat Liver Transplantation by Inducing Kupffer Cell M2 Polarization

Zhao, Zhenxing; Pan, Guangrui; Tang, Chengyong; Li, Zhongtang; Zheng, Daofeng; Wei, Xufu; Wu, Zhongjun

doi:10.1097/tp.0000000000002194

Cited by 45 publications

(44 citation statements)

References 57 publications

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“…Similarly, Zhao et al. found that IL‐34 was effective to inhibit acute rejection and prolong the recipients’ survival by altering the polarization of Kupffer cells polarization into an M2‐phenotype in a liver transplantation model in rats . Additionally, IL‐34 can be used as an ex vivo cytokine for the generation of immunosuppressive immune cells that can be utilized as adjuvant cell therapy to prolong survival of implanted grafts.…”

Section: Il‐34 From Bench To Bedsidementioning

confidence: 97%

“…In Kupffer cells, IL‐34 alters Kupffer cells polarization into an M2‐phenotype, characterized by decreased expression of pro‐inflammatory cytokines such as IL‐12, and increased expression of immunosuppressive cytokines, including Arg‐1, IL‐10, and TGF‐β1. The responsible mechanism was mediated by the IL‐34‐induced activation of the PI3K/Akt pathway, enhancement of the phosphorylation of mTOR, S6K, and 4E‐BP, and suppression of p65 and p38 MAPK activation …”

Section: Biological Functions Of Il‐34mentioning

confidence: 99%

See 1 more Smart Citation

Interleukin-34, a comprehensive review

Baghdadi

Umeyama

Hama

et al. 2018

Journal of Leukocyte Biology

117

120

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IL-34 is a novel cytokine that was identified in 2008 in a comprehensive proteomic analysis as a tissue-specific ligand of CSF-1 receptor (CSF-1R). IL-34 exists in all vertebrates including fish, amphibians, birds, and mammals, showing high conservation among species. Structurally, IL-34 belongs to the short-chain helical hematopoietic cytokine family but shows no apparent consensus structural domains, motifs, or sequence homology with other cytokines. IL-34 is synthesized as a secreted homodimeric glycoprotein that binds to the extracellular domains of CSF-1R and receptor-type protein-tyrosine phosphatase-zeta (PTP-ζ) in addition to the chondroitin sulfate chains of syndecan-1. These interactions result in activating several signaling pathways that regulate major cellular functions, including proliferation, differentiation, survival, metabolism, and cytokine/chemokine expression in addition to cellular adhesion and migration. In the steady state, IL-34 contributes to the development and maintenance of specific myeloid cell subsets in a tissue-specific manner: Langerhans cells in the skin and microglia in the brain. In pathological conditions, changes in IL-34 expression-increased or decreased-are involved in disease pathogenesis and correlate with progression, severity, and chronicity. One decade after its discovery, IL-34 has been introduced as a newcomer to the big family of interleukins with specific physiological functions, critical pathological roles, and promising clinical applications in disease diagnosis and treatment. In this review, we celebrate the 10th anniversary of IL-34 discovery, introducing its biological characteristics, and discussing the importance of IL-34 signaling network in health and disease.

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Section: Il‐34 From Bench To Bedsidementioning

confidence: 97%

Section: Biological Functions Of Il‐34mentioning

confidence: 99%

Interleukin-34, a comprehensive review

Baghdadi

Umeyama

Hama

et al. 2018

Journal of Leukocyte Biology

117

120

View full text Add to dashboard Cite

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“…Furthermore, macrophages differentiated from human peripheral blood monocytes with IL-34 exhibit greater resistance to HIV-1 infection than those derived from CSF1 due to increased expression of pertinent restriction factor genes 101 . IL-34 has also been demonstrated to repolarize rat M1 Kupffer cells (KCs) in the liver to the M2 phenotype by activating the PI3K/ protein kinase B/mammalian target of rapamycin (mTOR) pathway and could be used therapeutically to reduce acute rejection during liver transplantation 102 . Each of these ligands might play a different role in osteoclasts and other myeloid cells, which are discussed below.…”

Section: Csf1r Ligands and Their Differential Functions In Csf1r Signmentioning

confidence: 99%

The M-CSF receptor in osteoclasts and beyond

2020

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Colony-stimulating factor 1 receptor (CSF1R, also known as c-FMS) is a receptor tyrosine kinase. Macrophage colony-stimulating factor (M-CSF) and IL-34 are ligands of CSF1R. CSF1R-mediated signaling is crucial for the survival, function, proliferation, and differentiation of myeloid lineage cells, including osteoclasts, monocytes/macrophages, microglia, Langerhans cells in the skin, and Paneth cells in the intestine. CSF1R also plays an important role in oocytes and trophoblastic cells in the female reproductive tract and in the maintenance and maturation of neural progenitor cells. Given that CSF1R is expressed in a wide range of myeloid cells, altered CSF1R signaling is implicated in inflammatory, neoplastic, and neurodegenerative diseases. Inhibiting CSF1R signaling through an inhibitory anti-CSF1R antibody or small molecule inhibitors that target the kinase activity of CSF1R has thus been a promising therapeutic strategy for those diseases. In this review, we cover the recent progress in our understanding of the various roles of CSF1R in osteoclasts and other myeloid cells, highlighting the therapeutic applications of CSF1R inhibitors in disease conditions.

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“…In acute infection, overdose of hepatotoxic drugs, and liver IRI, KCs are activated by DAMPs via TLR3, TLR4, and TLR9 and polarized to the M1 phenotype, which induces proinflammatory cascades and infiltration of monocytes, neutrophils, and T lymphocytes, which exacerbate liver injury [26][27][28]. In our previous studies, we found that blocking the M1 KC polarization or promoting the KCs M2 polarization reduced liver IRI and organ rejection [18,29,30].…”

Section: Discussionmentioning

confidence: 97%

IL-4 Alleviates Ischaemia-Reperfusion Injury by Inducing Kupffer Cells M2 Polarization via STAT6-JMJD3 Pathway after Rat Liver Transplantation

Deng

Wang

et al. 2020

BioMed Research International

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Background. Liver ischaemia-reperfusion injury (IRI) remains a problem in liver transplantation. Interleukin-4 (IL-4) has been found to reduce liver IRI, but the exact mechanism remains unclear. Methods. Donor livers were infused with recombinant IL-4 or normal saline during cold storage, and the hepatocellular apoptosis and the inflammatory response were detected. The effect of IL-4 treatment on Kupffer cells (KCs) polarization and expression of the STAT6-JMJD3 pathway was evaluated in vivo and in vitro. KCs in donor livers were depleted by clodronate liposome treatment or JMJD3 was inhibited by GSK-J4 before liver transplantation to determine whether the protective effect of IL-4 treatment was dependent on KCs. Results. IL-4 treatment decreased sALT and sAST levels and alleviated hepatocellular apoptosis and inflammation at 6 h after liver transplantation. IL-4 treatment induced KCs alternatively activated (M2) polarization in vitro and in vivo, and the expression of STAT6 and JMJD3 was increased. JMJD3 knockdown abolished KCs M2 polarization and reduced the antiapoptotic and anti-inflammatory effects induced by IL-4 treatment in vitro. In addition, the protection of IL-4 treatment against IRI induced by liver transplantation was significantly reduced after the depletion of KCs or the inhibition of JMJD3 in donor livers. Conclusions. IL-4 treatment-induced KCs M2 polarization was dependent on the STAT6-JMJD3 pathway and protected liver grafts from IRI after liver transplantation.

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IL-34 Inhibits Acute Rejection of Rat Liver Transplantation by Inducing Kupffer Cell M2 Polarization

Abstract: IL-34 plays an important role in KC M2 polarization-dependent AR inhibition of rat liver transplantation.

Cited by 45 publications

References 57 publications

Interleukin-34, a comprehensive review

Interleukin-34, a comprehensive review

The M-CSF receptor in osteoclasts and beyond

IL-4 Alleviates Ischaemia-Reperfusion Injury by Inducing Kupffer Cells M2 Polarization via STAT6-JMJD3 Pathway after Rat Liver Transplantation

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