Quality-controlled characterization of a monoclonal antibody specific to an EC5-domain of human desmoglein 3 for pemphigus research.

Background: Pemphigus vulgaris (PV) is a life-threatening autoimmune blistering disease caused mainly by IgG autoantibodies (auto-abs) against the cadherin-type adhesion molecules desmoglein (Dsg) 1 and 3. Pathogenic anti-Dsg3 auto-abs bind to different Dsg3 epitopes, leading, among others, to signalling that is involved in pathogenic events, such as Dsg3 depletion. As central tools in research on PV, a limited number of antibodies such as AK23 are frequently used by the autoimmune bullous disease community.

A type I interferon regulatory network for human plasmacytoid dendritic cells based on heparin, membrane-bound and soluble BDCA-2.

Plasmacytoid dendritic cells (pDCs) produce type I interferons (IFNs) after sensing viral/bacterial RNA or DNA by toll-like receptor (TLR) 7 or TLR9, respectively. However, aberrant pDCs activation can cause adverse effects on the host and contributes to the pathogenesis of type I IFN-related autoimmune diseases. Here, we show that heparin interacts with the human pDCs-specific blood dendritic cell antigen 2 (BDCA-2) but not with related lectins such as DCIR or dectin-2.

Cholangiocytes Modulate CD100 Expression in the Liver and Facilitate Pathogenic T-Helper 17 Cell Differentiation.

Background & Aims: Chronic inflammation surrounding bile ducts contributes to the disease pathogenesis of most cholangiopathies. Poor efficacy of immunosuppression in these conditions suggests biliary-specific pathologic principles. Here we performed biliary niche specific functional interpretation of a causal mutation (CD100 K849T) of primary sclerosing cholangitis (PSC) to understand related pathogenic mechanisms.

Type 2 T-Cell Responses against Distinct Epitopes of the Desmoglein 3 Ectodomain in Pemphigus Vulgaris.

Pemphigus vulgaris (PV) is an autoimmune blistering disorder of the skin and/or mucous membranes caused by IgG autoantibodies that predominantly target two transmembrane desmosomal cadherins: desmoglein (DSG)1 and DSG3. DSG-specific T cells play a central role in PV pathogenesis because they provide help to autoreactive B cells for autoantibody production. In this study, we characterized DSG3-specific peripheral T cells in a cohort of 52 patients with PV and 41 healthy controls with regard to cytokine profile and epitope specificity.

Isolation of Lymphocytes from Human Skin and Murine Tissues: A Rapid and Epitope-Preserving Approach.

Tissue-resident immune cells have been shown to play an important role in skin health and disease. However, owing to limited access to human skin samples and time-consuming, technically demanding protocols, the characterization of tissue-derived cells remains challenging. For this reason, blood-derived leukocytes are frequently used as a surrogate specimen, although they do not necessarily reflect local immune responses in the skin.

Mucosal-associated invariant T-cell tumor infiltration predicts long-term survival in cholangiocarcinoma.

Background And Aims: Cholangiocarcinoma (CCA) is a malignancy arising from biliary epithelial cells of intra- and extrahepatic bile ducts with dismal prognosis and few nonsurgical treatments available. Despite recent success in the immunotherapy-based treatment of many tumor types, this has not been successfully translated to CCA. Mucosal-associated invariant T (MAIT) cells are cytotoxic innate-like T cells highly enriched in the human liver, where they are located in close proximity to the biliary epithelium.

Detection of autoreactive CD4+ T cells by MHC class II multimers in HLA-linked human autoimmune diseases.

Recognition of self-peptides in association with distinct HLA class II alleles by autoreactive CD4+ T cells is central for loss of immunological tolerance leading to autoimmune disease. However, identifying immunodominant self-peptides and characterizing autoreactive T cells is challenging. In this issue of the JCI, Falta et al.

Immune serological diagnosis of pemphigus.

Pemphigus is a rare autoimmune blistering disease which manifests with painful erosions and blisters of the skin and mucosa. This disorder is caused by autoantibodies attacking desmosomal proteins, necessary for cell-cell contact stability and epidermal integrity. Desmoglein (Dsg) 1 and Dsg3 are the two major target antigens in pemphigus.

The cytokine profile of menstrual blood.

Introduction: The menstrual cycle is regulated by a complex interplay between endometrial epithelial cells, endothelial cells, immune cells, and sex hormones. To communicate, cells secrete cytokines that have multiple and diverse effects on recipient cells. Knowledge of how these cells interact in the uterus is insufficient.

Methods for High-Dimensional Flow Cytometry Analysis of Human MAIT Cells in Tissues and Peripheral Blood.

Mucosal-associated invariant T (MAIT) cells can be found throughout the human body, in peripheral blood, at mucosal sites, and, among other organs, in the liver. As unconventional T cells, MAIT cells have the capacity to readily respond to bacterial infections and are also engaged during anti-viral responses. To thoroughly investigate the MAIT cell phenotype and function in such conditions, multi-color flow cytometry is an appropriate and powerful tool.

NK cells are activated and primed for skin-homing during acute dengue virus infection in humans.

Despite animal models showing that natural killer (NK) cells are important players in the early defense against many viral infections, the NK cell response is poorly understood in humans. Here we analyze the phenotype, temporal dynamics, regulation and trafficking of NK cells in a patient cohort with acute dengue virus infection. NK cells are robustly activated and proliferate during the first week after symptom debut.

Hantavirus Inhibits TRAIL-Mediated Killing of Infected Cells by Downregulating Death Receptor 5.

Cytotoxic lymphocytes normally kill virus-infected cells by apoptosis induction. Cytotoxic granule-dependent apoptosis induction engages the intrinsic apoptosis pathway, whereas death receptor (DR)-dependent apoptosis triggers the extrinsic apoptosis pathway. Hantaviruses, single-stranded RNA viruses of the order Bunyavirales, induce strong cytotoxic lymphocyte responses in infected humans.

Imbalance of Genes Encoding Natural Killer Immunoglobulin-Like Receptors and Human Leukocyte Antigen in Patients With Biliary Cancer.

Background & Aims: Bile duct tumors are rare and have poor prognoses. Natural killer (NK) cells are frequent in human liver and infiltrate these tumors but do not control their progression. Responses of NK cells are regulated by NK immunoglobulin-like receptors (KIRs), which interact with HLA class I ligands.

Retained NK Cell Phenotype and Functionality in Non-alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD), and the progressive stage non-alcoholic steatohepatitis (NASH), is the predominant cause of chronic liver disease globally. As part of the complex pathogenesis, natural killer (NK) cells have been implicated in the development of liver inflammation in experimental murine models of NASH. However, there is a lack of knowledge on how NK cells are affected in humans with this disease.

Chronic hepatitis delta virus infection leads to functional impairment and severe loss of MAIT cells.

Background & Aims: Hepatitis delta virus (HDV) infection is the most severe form of viral hepatitis. Although HDV-associated liver disease is considered immune-mediated, adaptive immune responses against HDV are weak. Thus, the role of several other cell-mediated mechanisms such as those driven by mucosa-associated invariant T (MAIT) cells, a group of innate-like T cells highly enriched in the human liver, has not been extensively studied in clinical HDV infection.

Primary sclerosing cholangitis leads to dysfunction and loss of MAIT cells.

Primary sclerosing cholangitis (PSC) is a severe chronic liver disease of the small and large bile ducts. The pathogenesis is unknown but a strong immune cell component has been suggested. Mucosal-associated invariant T (MAIT) cells are abundant in human liver and localize around bile ducts.

Hepatitis B virus-specific T cell responses after stopping nucleos(t)ide analogue therapy in HBeAg-negative chronic hepatitis B.

Background & Aims: Treatment with nucleos(t)ide analogues (NA) leads to hepatitis B virus (HBV) DNA suppression in most patients with chronic hepatitis B (CHB), but HBV surface antigen (HBsAg) loss rates are low. Upon NA discontinuation, HBV DNA can return rapidly with ensuing alanine aminotransferase flares and induction of cytokines. Several studies reported higher HBsAg loss rates after stopping therapy, but at present it is unclear if cell-mediated immune responses are altered after treatment discontinuation.

Increased NK Cell Function After Cessation of Long-Term Nucleos(t)ide Analogue Treatment in Chronic Hepatitis B Is Associated With Liver Damage and HBsAg Loss.

Background: Treatment with nucleos(t)ide analogues (NA) suppresses hepatitis B virus (HBV) DNA but rarely leads to functional cure of chronic hepatitis B (CHB). Following NA cessation, some hepatitis B e antigen (HBeAg)-negative CHB patients experience hepatitis B s antigen (HBsAg) loss. Cellular immune responses, including natural killer (NK) cell responses, explaining virological events following NA treatment cessation remain elusive.

Lactobacilli regulate Staphylococcus aureus 161:2-induced pro-inflammatory T-cell responses in vitro.

There seems to be a correlation between early gut microbiota composition and postnatal immune development. Alteration in the microbial composition early in life has been associated with immune mediated diseases, such as autoimmunity and allergy. We have previously observed associations between the presence of lactobacilli and Staphylococcus (S.

RNA delivery by heat shock protein-70 into mammalian cells: a preliminary study.

Heat shock proteins (Hsps) are ubiquitous molecular chaperones with indispensable roles in assisting protein folding and giving protection from proteotoxic environmental harm. Members of the 70-kDa heat shock protein family have been demonstrated to recognize and bind with distinguished RNA sequences, which function as determinants of eukaryotic mRNA stability. We have earlier identified the molecular domains involved in RNA-binding and characterized in detail the specificity, affinity and some regulatory aspects of this molecular interaction using various deletion mutants and homologues of Hsp70.

A scope-of-practice survey leading to the development of standards of practice for health promotion in higher education.

To review and analyze the scope of practice of health promotion services and draft standards of quality indicators for higher education communities, the American College Health Association (ACHA) initiated a Task Force on Health Promotion in Higher Education in May 1996. Members of the task force developed a National Survey on Health Promotion and Education in Institutions of Higher Education and mailed the survey to a stratified random sample of 600 ACHA member institutions, as well as to 97 key "best-practice health promotion leaders". The larger sample produced a 75.

The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochore-microtubule attachment and in maintaining the spindle assembly checkpoint.

The proper segregation of sister chromatids in mitosis depends on bipolar attachment of all chromosomes to the mitotic spindle. We have identified the small molecule Hesperadin as an inhibitor of chromosome alignment and segregation. Our data imply that Hesperadin causes this phenotype by inhibiting the function of the mitotic kinase Aurora B.