Search results for "Unity"

An innate cell-mediated, murine ulcerative colitis-like syndrome in the absence of nuclear factor of activated T cells.

2004

Abstract Background & Aims: Nuclear factor of activated T cells transcription factors plays a central role in immunity by regulating the expression of multiple cytokines and other regulatory molecules, many of which have been heavily implicated in the pathogenesis of inflammatory bowel disease. However, few studies have directly investigated the nuclear factor of activated T cells proteins in inflammatory bowel disease. We describe here a specific role for nuclear factor of activated T cells c2 in the pathogenesis of murine inflammatory bowel disease. Methods: Mice deficient for nuclear factor of activated T cells c2, recombinase activating gene-2, or both and transgenic or nontransgenic fo…

CD4+CD25+ regulatory T cells suppress mast cell degranulation and allergic responses through OX40-OX40L interaction.

2008

T regulatory (Treg) cells play a role in the suppression of immune responses, thus serving to induce tolerance and control autoimmunity. Here, we explored whether Treg cells influence the immediate hypersensitivity response of mast cells (MCs). Treg cells directly inhibited the FcεRI-dependent MC degranulation through cell-cell contact involving OX40-OX40L interactions between Treg cells and MCs, respectively. When activated in the presence of Treg cells, MCs showed increased cyclic adenosine monophosphate (cAMP) concentrations and reduced Ca2+ influx, independently of phospholipase C (PLC)-γ2 or Ca2+ release from intracellular stores. Antagonism of cAMP in MCs reversed the inhibitory effec…

Autoimmunity and liver disease

1990

Regulation of T-cell apoptosis in inflammatory bowel disease: to die or not to die, that is the mucosal question.

2001

T-cell resistance against apoptosis contributes to inappropriate T-cell accumulation and the perpetuation of chronic mucosal inflammation in inflammatory bowel diseases (IBDs). Anti-interleukin-12 (IL-12) and anti-IL-6 receptor antibodies suppress colitis activity by the induction of T-cell apoptosis. These findings have important implications for the design of effective treatment regimens in IBD.

Synergistic activation of dendritic cells by combined Toll-like receptor ligation induces superior CTL responses in vivo.

2006

Toll-like receptors (TLRs) are able to interact with pathogen-derived products and their signals induce the coordinated activation of innate and adaptive immune mechanisms. Dendritic cells (DCs) play a central role in these events. As the different TLRs are able to trigger MyD88/TRIF-dependent and -independent signaling pathways, we wondered if the simultaneous activation of these signaling cascades would synergize with respect to DC activation and induce superior cytotoxic T-lymphocyte (CTL) activity in vivo. We observed that indeed the combined activation of MyD88-dependent and -independent signaling induced by TLR7 and TLR3 ligands provoked a more rapid and more sustained bone marrow–der…

Tolerance without clonal expansion: self-antigen-expressing B cells program self-reactive T cells for future deletion.

2008

Abstract B cells have been shown in various animal models to induce immunological tolerance leading to reduced immune responses and protection from autoimmunity. We show that interaction of B cells with naive T cells results in T cell triggering accompanied by the expression of negative costimulatory molecules such as PD-1, CTLA-4, B and T lymphocyte attenuator, and CD5. Following interaction with B cells, T cells were not induced to proliferate, in a process that was dependent on their expression of PD-1 and CTLA-4, but not CD5. In contrast, the T cells became sensitive to Ag-induced cell death. Our results demonstrate that B cells participate in the homeostasis of the immune system by abl…

The problems and promises of research into human immunology and autoimmune disease

2012

Translational research in autoimmunity is hampered by a number of hurdles, including a lack of knowledge regarding initiating and pathologically relevant autoantigens, the low frequency of autoreactive pathogenic B and T cells, difficulty in accessing the affected tissue, differences between self-reactive and pathogen-specific lymphocytes, a lack of etiologically relevant preclinical animal models and the heterogeneity of disease presentation. Given the need for biomarkers and new therapeutics, it is imperative that these hurdles be surmounted.

Host immune response to Cryptosporidium parvum infection

2010

Species of the genus Cryptosporidium are protozoan parasites (Apicomplexa) that cause gastroenteritis in animals and humans. Of these Cryptosporidium parvum and Cryptosporidium hominis are the major causative agents of human cryptosporidiosis. Whereas infection is self-limiting in the immunocompetent hosts, immunocompromised individuals develop a chronic, life-threatening disease. As specific therapeutic or preventive interventions are not yet available, better understanding of the immune response to the parasite is required. This minireview briefly summarizes the factors involved in the innate and acquired immune response in this pathogen-host interaction with an emphasis on more recent da…

The Mitochondrial Targeting Chaperone 14-3-3ε Regulates a RIG-I Translocon that Mediates Membrane Association and Innate Antiviral Immunity

2012

SummaryRIG-I is a cytosolic pathogen recognition receptor that initiates immune responses against RNA viruses. Upon viral RNA recognition, antiviral signaling requires RIG-I redistribution from the cytosol to membranes where it binds the adaptor protein, MAVS. Here we identify the mitochondrial targeting chaperone protein, 14-3-3ε, as a RIG-I-binding partner and essential component of a translocation complex or “translocon” containing RIG-I, 14-3-3ε, and the TRIM25 ubiquitin ligase. The RIG-I translocon directs RIG-I redistribution from the cytosol to membranes where it mediates MAVS-dependent innate immune signaling during acute RNA virus infection. 14-3-3ε is essential for the stable inte…

Transformation Of Individual Learning Into Organisational And Networked Learning In Vocational Education

2008

The Finnish vocational education and training system has traditionally been largely school-based with the inclusion of only short practice periods in students’ study programmes. In 2001 the system was reformed, new 3-year study programmes were introduced in all fields of study, and workplace learning (WPL; at least 6 months) became a compulsory part of all vocational study programmes. WPL is defined as systematically guided and assessed learning that takes place in authentic work environments. Thus, workplaces have to provide guidance and support for student learning and to participate in a tripartite assessment. At the beginning of the workplace learning period the student, the teacher and…