Differences in F pocket impact on HLA I genetic associations with autoimmune diabetes.

Introduction: Human leukocyte antigen (HLA) I molecules present antigenic peptides to activate CD8 T cells. Type 1 Diabetes (T1D) is an auto-immune disease caused by aberrant activation of the CD8 T cells that destroy insulin-producing pancreatic β cells. Some alleles were shown to increase the risk of T1D (T1D-predisposing alleles), while some reduce this risk (T1D-protective alleles).

Polymorphism in F pocket affects peptide selection and stability of type 1 diabetes-associated HLA-B39 allotypes.

HLA-B*39:06, HLA-B*39:01, and HLA-B*38:01 are closely related HLA allotypes differentially associated with type 1 diabetes (T1D) risk and progression. B*39:06 is highly predisposing, while B*39:01 and B*38:01 are weakly predisposing and protective allotypes, respectively. Here, we aimed to decipher molecular mechanisms underlying the differential association of these allotypes with T1D pathogenesis.

Translocated HMGB3 is involved in papillary thyroid cancer progression by activating cytoplasmic TLR3 and transmembrane TREM1.

The family of high mobility group box (HMGB) proteins participates in various biological processes including immunity, inflammation, as well as cancer formation and progression. However, its role in thyroid cancer remains to be clarified. We performed quantitative RT-PCR (qRT-PCR), western blot, enzyme-linked immunosorbent, immunohistochemistry, and immunofluorescence assays to evaluate the expression level and subcellular location of HMGB3.

Fecal microbiota transplantation enhances cell therapy in a rat model of hypoganglionosis by SCFA-induced MEK1/2 signaling pathway.

Hirschsprung disease (HSCR), one of several neurocristopathies in children, is characterized by nerve loss in the large intestine and is mainly treated by surgery, which causes severe complications. Enteric neural crest-derived cell (ENCC) transplantation is a potential therapeutic strategy; however, so far with poor efficacy. Here, we assessed whether and how fecal microbiota transplantation (FMT) could improve ENCC transplantation in a rat model of hypoganglionosis; a condition similar to HSCR, with less intestinal innervation.

Intrinsic Folding Properties of the HLA-B27 Heavy Chain Revealed by Single Chain Trimer Versions of Peptide-Loaded Class I Major Histocompatibility Complex Molecules.

Peptide-loaded Major Histocompatibility Complex (pMHC) class I molecules can be expressed in a single chain trimeric (SCT) format, composed of a specific peptide fused to the light chain beta-2 microglobulin (β2m) and MHC class I heavy chain (HC) by flexible linker peptides. pMHC SCTs have been used as effective molecular tools to investigate cellular immunity and represent a promising vaccine platform technology, due to their intracellular folding and assembly which is apparently independent of host cell folding pathways and chaperones. However, certain MHC class I HC molecules, such as the Human Leukocyte Antigen B27 (HLA-B27) allele, present a challenge due to their tendency to form HC aggregates.

Inter-ankle Systolic Blood Pressure Difference Is a Marker of Increased Fasting Blood-Glucose in Asian Pregnant Women.

Objective: This cross-sectional study aimed to determine the relationship between clinical blood pressures and blood pressures measured using Doppler with blood glucose in pregnancy by ethnicity.

Methods: We recruited 179 (52% White European, 48% Asian) pregnant women at 24-28 weeks of gestation who underwent a glucose tolerance test in an antenatal clinic in Bradford Royal Infirmary, the UK, from 2012 to 2013. Systolic blood pressures in the arm (left and right brachial) and ankle [left and right posterior tibial (PT) and dorsalis pedalis (DP)] blood pressures were measured using a Doppler probe.

Genetic contributions of MHC class I antigen processing and presentation pathway to bladder cancer risk and recurrence.

Human leukocyte antigen class I (HLA class I) antigen processing and presentation pathway (APP) defines anti-tumor immune response. ERAP, TAP, tapasin (TAPBP), and IFNγ modulate APP: control HLA class I expression in the tumor and the repertoire of presented tumor antigens. At the same time, vascular endothelial growth factor (VEGF) acts as an immunomodulator in the tumor microenvironment.

Targeting Small GTPases and Their Prenylation in Diabetes Mellitus.

A fundamental role of pancreatic β-cells to maintain proper blood glucose level is controlled by the Ras superfamily of small GTPases that undergo post-translational modifications, including prenylation. This covalent attachment with either a farnesyl or a geranylgeranyl group controls their localization, activity, and protein-protein interactions. Small GTPases are critical in maintaining glucose homeostasis acting in the pancreas and metabolically active tissues such as skeletal muscles, liver, or adipocytes.

Marriage contributes to higher obesity risk in China: findings from the China Health and Nutrition Survey.

Background: To investigate the association between marriage and the prevalence of overweight and obesity in China.

Methods: We conducted cross-sectional and retrospective cohort analyses using a nationwide sample of 36,310 individuals from the China Health and Nutrition Survey [2004-2015].

Results: The prevalence of overweight and obesity increased from 28.

The Fecal Microbiota Is Already Altered in Normoglycemic Individuals Who Go on to Have Type 2 Diabetes.

Objective: Mounting evidence has suggested a link between gut microbiome characteristics and type 2 diabetes (T2D). To determine whether these alterations occur before the impairment of glucose regulation, we characterize gut microbiota in normoglycemic individuals who go on to develop T2D.

Methods: We designed a nested case-control study, and enrolled individuals with a similar living environment.

Hepatoprotective effect of apolipoprotein A4 against carbon tetrachloride induced acute liver injury through mediating hepatic antioxidant and inflammation response in mice.

Apolipoprotein A4 (ApoA4) regulates lipid and glucose metabolism and exerts anti-inflammatory effects in atherogenesis and colitis. The present study explored the presumed protective role of ApoA4 in carbon tetrachloride (CCl4)-induced acute liver injury (ALI) in mice. The ALI model in wild type (WT), ApoA4 knock-out (ApoA4-KO) and ApoA4 transgenic (ApoA4-TG) mice was induced by a single intraperitoneal administration of CCl4.

Recurrent bladder cancer in aging societies: Importance of major histocompatibility complex class I antigen presentation.

Aging is associated with an insufficient immune response that may lead to the initiation and progression of various malignancies. Bladder cancer (BC), prevalent in elderly patients, predominantly presents as recurrent nonmuscle invasive BC that requires further treatment. There is much interest in the activation of patients' immune cells with the focus on CD8+ T cells.

Chemokines and their receptors promoting the recruitment of myeloid-derived suppressor cells into the tumor.

Myeloid-derived suppressor cells (MDSCs) expand in tumor-bearing host. They suppress anti-tumor immune response and promote tumor growth. Chemokines play a vital role in recruiting MDSCs into tumor tissue.

Production and Thermal Exchange of Conditional Peptide-MHC I Multimers.

Cytotoxic CD8 T cells mediate cellular immunity through recognition of specific antigens presented by MHC class I on all nucleated cells. Studying T cell interactions and responses provides invaluable information on infection, autoimmunity and cancer. Fluorescently labeled multimers of MHC I can be used to quantify, characterize, and isolate specific CD8 T cells by flow cytometry.

Epithelial C5aR1 Signaling Enhances Uropathogenic Adhesion to Human Renal Tubular Epithelial Cells.

Recent work in a murine model of ascending urinary tract infection has suggested that C5a/C5aR1 interactions play a pathogenic role in the development of renal infection through enhancement of bacterial adhesion/colonization to renal tubular epithelial cells (RTECs). In the present study, we extended these observations to human. We show that renal tubular epithelial C5aR1 signaling is involved in promoting uropathogenic (UPEC) adhesion/invasion of host cells.

A flexible MHC class I multimer loading system for large-scale detection of antigen-specific T cells.

Adaptive immunity is initiated by T cell recognition of specific antigens presented by major histocompatibility complexes (MHCs). MHC multimer technology has been developed for the detection, isolation, and characterization of T cells in infection, autoimmunity, and cancer. Here, we present a simple, fast, flexible, and efficient method to generate many different MHC class I (MHC I) multimers in parallel using temperature-mediated peptide exchange.

Serum levels of adipokines and cytokines in psoriasis patients: a systematic review and meta-analysis.

Purpose: To evaluate the association of serum levels of adipokines and cytokines with psoriasis.

Materials And Methods: A comprehensive literature search was performed in PubMed, ScienceDirect and Web of Science for the available relevant studies published before December 1, 2016. Differences in serum marker levels between patients and controls were pooled as standardized mean differences (SMDs) with 95% confidence interval to combine the effect estimations.

Corrigendum to "The Controversial C5a Receptor C5aR2: Its Role in Health and Disease".

[This corrects the article DOI: 10.1155/2017/8193932.].

The Controversial C5a Receptor C5aR2: Its Role in Health and Disease.

After the discovery of the C5a receptor C5aR1, C5aR2 is the second receptor found to bind C5a and its des-arginine form. As a heptahelical G protein-coupled receptor but devoid of the intracellular G signal, C5aR2 is special and confusing. Ramifications and controversies about C5aR2 are under debate since its identification, from putative ligands and cellular localization to intracellular signals and pathological roles in inflammation and immunity.

An ER-Associated Pathway Defines Endosomal Architecture for Controlled Cargo Transport.

Through a network of progressively maturing vesicles, the endosomal system connects the cell's interior with extracellular space. Intriguingly, this network exhibits a bilateral architecture, comprised of a relatively immobile perinuclear vesicle "cloud" and a highly dynamic peripheral contingent. How this spatiotemporal organization is achieved and what function(s) it curates is unclear.

The first step of peptide selection in antigen presentation by MHC class I molecules.

MHC class I molecules present a variable but limited repertoire of antigenic peptides for T-cell recognition. Understanding how peptide selection is achieved requires mechanistic insights into the interactions between the MHC I and candidate peptides. We find that, at first encounter, MHC I H-2K(b) considers a wide range of peptides, including those with expanded N termini and unfitting anchor residues.

How to target MHC class II into the MIIC compartment.

Major histocompatibility complex (MHC) class II molecules (MHC II) present exogenous antigens to CD4+ T cells to modulate immune responses. To contact these antigens, MHC II is delivered to the late endosomal MHC class II compartment (MIIC). This compartment has a complex architecture and consists of internal membranes or vesicles surrounded by a limiting membrane.

Tapasin dependence of major histocompatibility complex class I molecules correlates with their conformational flexibility.

Major histocompatibility complex (MHC) class I molecules present cell internally derived peptides at the plasma membrane for surveillance by cytotoxic T lymphocytes. The surface expression of most class I molecules at least partially depends on the endoplasmic reticulum protein, tapasin, which helps them to bind peptides of the right length and sequence. To determine what makes a class I molecule dependent on support by tapasin, we have conducted in silico molecular dynamics (MD) studies and laboratory experiments to assess the conformational state of tapasin-dependent and -independent class I molecules.

EBV protein BNLF2a exploits host tail-anchored protein integration machinery to inhibit TAP.

EBV, the prototypic human γ(1)-herpesvirus, persists for life in infected individuals, despite the presence of vigorous antiviral immunity. CTLs play an important role in the protection against viral infections, which they detect through recognition of virus-encoded peptides presented in the context of HLA class I molecules at the cell surface. The viral peptides are generated in the cytosol and are transported into the endoplasmic reticulum (ER) by TAP.