Gasdermin D-mediated pyroptosis is regulated by AMPK-mediated phosphorylation in tumor cells.

Gasdermin D (GSDMD) is a critical mediator of pyroptosis, which consists of a N-terminal pore-forming domain and a C-terminal autoinhibitory domain. Its cytolytic activity is sequestered by the intramolecular autoinhibitory mechanism. Upon caspase-1/11 mediated cleavage of GSDMD, the N-terminal pore-forming domain (GD-NT) is released to mediate pyroptosis.

Abnormal mechanical stress on bicuspid aortic valve induces valvular calcification and inhibits Notch1/NICD/Runx2 signal.

Background: Bicuspid aortic valve (BAV) is a congenital cardiac deformity, increasing the risk of developing calcific aortic valve disease (CAVD). The disturbance of hemodynamics can induce valvular calcification, but the mechanism has not been fully identified.

Methods: We constructed a finite element model (FEM) of the aortic valve based on the computed tomography angiography (CTA) data from BAV patients and tricuspid aortic valve (TAV) individuals.

Adenovirus-IL-10 relieves chronic rejection after mouse heart transplantation by inhibiting miR-155 and activating SOCS5.

Chronic rejection remains the main factor that influence long-term survival of patients after heart transplantation. Interleukin-10 (IL-10) play critical role in macrophages-mediated transplant immune responses. We investigated the mechanism of IL-10 in macrophage related chronic rejection after mouse heart transplantation.

The Expansion of Myeloid-Derived Suppressor Cells Correlates With the Severity of Pneumonia in Kidney Transplant Patients.

Background: Pneumonia is one of the most frequent but serious infectious complications post kidney transplantation. Severe pneumonia induces sustained immunosuppression, but few parameters concerning immune status are used to assess the severity of pneumonia. Myeloid-derived suppressor cells (MDSCs) are induced under infection and have the strong immunosuppressive capacity, but the correlation between MDSCs and pneumonia in kidney transplant recipients (KTRs) is unknown.

Identification and Verification of Tumor Immune Microenvironment-Related Prognostic Genes in Kidney Renal Clear Cell Carcinoma.

Background: The tumor immune microenvironment is vital to kidney renal clear cell carcinoma (KIRC) progression, and immunotherapies have been shown to be effective in the management of KIRC. However, the prognostic genes associated with the tumor immune microenvironment in KIRC have not been fully identified. We obtained the KIRC RNA sequencing data and the clinical characteristics from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) database.

Genetically targeting the BATF family transcription factors BATF and BATF3 in the mouse abrogates effector T cell activities and enables long-term heart allograft survival.

T cells must be activated and become effectors first before executing allograft rejection, a process that is regulated by diverse signals and transcription factors. In this study, we studied the basic leucine zipper ATF-like transcription factor (BATF) family members in regulating T cell activities in a heart transplant model and found that mice deficient for both BATF and BATF3 (Batf Batf3 mice) spontaneously accept the heart allografts long-term without tolerizing therapies. Similarly, adoptive transfer of wild type T cells into Rag1 hosts induced prompt rejection of heart and skin allografts, whereas the Batf Batf3 T cells failed to do so.

Transgenic Expression of a Mutant Ribonuclease Regnase-1 in T Cells Disturbs T Cell Development and Functions.

Regnase-1 is an RNA-binding protein with ribonuclease activities, and once induced it controls diverse immune responses by degrading mRNAs that encode inflammatory cytokines and costimulatory molecules, thus exerting potent anti-inflammatory functions. However, Regnase-1 is extremely sensitive to degradation by proteases and therefore short-lived. Here, we constructed a mutant Regnase-1 that is resistant to degradation and expressed this mutant as a transgene specifically in T cells.

Erythropoietin and its derivatives: from tissue protection to immune regulation.

Erythropoietin (EPO) is an evolutionarily conserved hormone well documented for its erythropoietic role via binding the homodimeric EPO receptor (EPOR). In past decades, evidence has proved that EPO acts far beyond erythropoiesis. By binding the tissue-protective receptor (TPR), EPO suppresses proinflammatory cytokines, protects cells from apoptosis and promotes wound healing.

Adaptive features of innate immune cells and their relevance to graft rejection.

Purpose Of Review: Allograft rejection involves both innate and adaptive immune cells, and the adaptive immune cells have dominated transplant studies for decades. Recent studies have identified surprising new features for the innate immune cells, including memory recall responses, which may have significant implications in further improvement of transplant outcomes.

Recent Findings: Transplant survival is excellent in the short-term, but the long-term graft outcomes are not so, and most grafts are continuously lost to chronic rejection in the clinic.

Identification of the E3 Ligase TRIM29 as a Critical Checkpoint Regulator of NK Cell Functions.

NK cells play an important role in immune surveillance and protective immunity, mainly through rapid cytokine release and cytolytic activities. But how such responses are negatively regulated remains poorly defined. In this study, we demonstrated that the E3 ubiquitin ligase TRIM29 is a crucial regulator of NK cell functions.