The presence of post-translational regulation of MHC class II (MHC II) under physiological conditions has been demonstrated recently in dendritic cells (DCs) that potently function as antigen-presenting cells (APCs). Here, we report that MARCH-I, an E3 ubiquitin ligase, plays a pivotal role in the post-translational regulation of MHC II in B cells. MARCH-I expression was particularly high in B cells, and the forced expression of MARCH-I induced the ubiquitination of MHC II. In B cells from MARCH-I-deficient mice (MARCH-I KO), the half-life of surface MHC II was prolonged and the ubiquitinated form of MHC II completely disappeared. In addition, MARCH-I-deficient B cells highly expressed exogenous antigen-loaded MHC II on their surface and showed high ability to present exogenous antigens. These results suggest that the function of MHC II in B cells is regulated through ubiquitination by MARCH-I.
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http://dx.doi.org/10.1038/sj.emboj.7601556 | DOI Listing |
Vet Sci
December 2024
College of Veterinary Medicine, Yangzhou University/Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou 225009, China.
This study investigated the effects of long-term serum starvation on autophagy, metabolism, and differentiation of porcine skeletal muscle satellite cells (SMSCs) and elucidated the role of autophagy in skeletal muscle development. Our findings provide a theoretical basis for improving meat production in domestic pigs. The SMSCs isolated and preserved in our laboratory were revived and divided into six groups based on the culture medium serum concentration to simulate varying levels of serum starvation: 20% serum (control group), 15% serum (mild serum starvation group), 5% serum (severe serum starvation group), and their autophagy inhibition groups supplemented with 3-methyladenine.
View Article and Find Full Text PDFCells
January 2025
Department of Physiology, College of Medicine, Hallym University, Chuncheon 24252, Republic of Korea.
Phosphodiesterase (PDE) enzymes regulate intracellular signaling pathways crucial for brain development and the pathophysiology of neurological disorders. Among the 11 PDE subtypes, PDE4 and PDE5 are particularly significant due to their regulation of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) signaling, respectively, which are vital for learning, memory, and neuroprotection. This review synthesizes current evidence on the roles of PDE4 and PDE5 in neurological health and disease, focusing on their regulation of second messenger pathways and their implications for brain function.
View Article and Find Full Text PDFNat Commun
January 2025
Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN, USA.
The inherent antigen cross-reactivity of the T cell receptor (TCR) is balanced by high specificity. Surprisingly, TCR specificity often manifests in ways not easily interpreted from static structures. Here we show that TCR discrimination between an HLA-A*03:01 (HLA-A3)-restricted public neoantigen and its wild-type (WT) counterpart emerges from distinct motions within the HLA-A3 peptide binding groove that vary with the identity of the peptide's first primary anchor.
View Article and Find Full Text PDFCell Host Microbe
January 2025
Department of Pathology and Immunology, Washington University School of Medicine in St. Louis, Saint Louis, MO 63110, USA. Electronic address:
Here, we explore the relationship between dietary fibers, colonic epithelium major histocompatibility complex class II (MHC-II) expression, and immune cell interactions in regulating susceptibility to Clostridioides difficile infection (CDI). We find that a low-fiber diet increases MHC-II expression in the colonic epithelium, which, in turn, worsens CDI by promoting the development of pathogenic CD4 intraepithelial lymphocytes (IELs). The influence of dietary fibers on MHC-II expression is mediated by its metabolic product, acetate, and its receptor, free fatty acid receptor 2 (FFAR2).
View Article and Find Full Text PDFClin Epigenetics
January 2025
School of Biomedical Sciences and Pharmacy, The University of Newcastle, Callaghan, NSW, 2308, Australia.
Background: Hypomethylating agents (HMA), such as azacytidine (AZA) and decitabine (DAC), are epigenetic therapies used to treat some patients with acute myeloid leukaemia (AML) and myelodysplastic syndrome. HMAs act in a replication-dependent manner to remove DNA methylation from the genome. However, AML cells targeted by HMA therapy are often quiescent within the bone marrow, where oxygen levels are low.
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