Details

Autor(en) / Beteiligte

• Chen, Yajun
• He, Yiping
• Wu, Xinyi
• Xu, Xuesong
• Gong, Junhua
• Chen, Yong
• Gong, Jianping

Titel

Rubicon promotes the M2 polarization of Kupffer cells via LC3-associated phagocytosis-mediated clearance to improve liver transplantation

Ist Teil von

• Cellular immunology, 2022-08, Vol.378, p.104556-104556, Article 104556

Ort / Verlag

Netherlands: Elsevier Inc

Erscheinungsjahr

2022

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• •We reported that Rubicon-mediated LAP promotes the degradation capability of KCs to clear apoptotic T lymphocytes.•We proved that PUFAs, the product of apoptotic T cell degradation, activates PPARγ which further promotes the M2 polarization of KCs. Enhanced degradation capability mediated by Rubicon is beneficial for improving the apoptotic cell clearance of AR and promoting M2 polarization of KCs. Acute rejection (AR) after liver transplantation (LT) is closely related to the survival of patients after surgery. Enhancement of the ability of Kupffer cells (KCs) to eliminate apoptotic cells can effectively alleviate AR. Rubicon lentivirus (LV) and Rubicon small interfering RNA (siRNA) were transfected into KCs extracted from the liver tissue of mice. Primary KCs were extracted and cocultured with zymosan and apoptotic T lymphocytes. The levels of CD86, CD163, IL-10, TNF-α, TGF-β, JAK1, STAT6, AKT1, mTOR and peroxisome proliferator–activated receptor-γ (PPARγ) were assessed via Western blotting (WB) and q-PCR. The levels of CD86 and CD163 were assessed via flow cytometry. mCherry-GFP-LC3 adenovirus (AV) was transfected into KCs. The recruitment of LC3II and the fusion of phagosomes and lysosomes were detected using immunofluorescence. Rubicon adeno-associated virus (AAV) was transfected into the liver tissue of mice via the portal vein, and models of immune tolerance (IT) and AR following LT were established. Pathological changes in the liver tissue were detected using HE staining. Apoptotic cells were assessed via TUNEL staining. The polarization state of KCs was detected via immunohistochemical staining. Rubicon-mediated LC3-associated phagocytosis (LAP) promotes the ability of KCs to degrade and clear apoptotic T lymphocytes. Polyunsaturated fatty acids (PUFAs), the product of apoptotic T lymphocyte degradation, activate PPARγ, which further promotes the M2 polarization of KCs. Enhanced degradation mediated by Rubicon contributes to promoting the M2 polarization of KCs and a microenvironment supportive of IT. Rubicon-mediated LAP promotes the clearance capability and M2 polarization of KCs via PUFA-dependent PPARγ activation to improve LT.