Biological functions of extracellular vesicles from mammalian cells.

Extracellular vesicles (EVs) are enclosed by a phospholipid bilayer and can be secreted by most types of cells. EVs deliver cargo from the secreting cell into the cytoplasm of recipient cells, influencing the function of the recipient cells. EVs are attracting increasing attention from a broad range of clinicians and scientists due to their ability to promote or inhibit various physiological pathways or pathological conditions.

Sex-dependent expression levels of VAV1 and P2X7 in PBMC of multiple sclerosis patients.

Multiple sclerosis (MS) is an inflammatory autoimmune disorder of the central nervous system and the leading cause of progressive neurological disability in young adults. It decreases the patient's lifespan by about 10 years and affects women more than men. No medication entirely restricts or reverses neurological degradation.

P2X7 purinergic receptor plays a critical role in maintaining T-cell homeostasis and preventing lupus pathogenesis.

The severe lymphoproliferative and lupus diseases developed by MRL/ mice depend on interactions between the Fas mutation and MRL genetic background. Thus, the Fas mutation causes limited disease in C57BL/6 mice. We previously found that accumulating B220 CD4CD8 double negative (DN) T cells in MRL/ mice show defective P2X7 receptor ( P2X7)-induced cellular functions, suggesting that P2X7 contributes to T-cell homeostasis, along with Fas.

The ins and outs of T cell signaling.

This special edition summarizes major advances in our understanding of signaling by T lymphocytes. T cell interactions with antigen-presenting cells (APCs) and other immune cells are characterized by changes in T cell adhesion and major rearrangements of the actin cytoskeleton. This issue describes some of the mediators of these changes both within the T cells and on the T cell surface.

Scaling the tips of the ALPS.

This special issue contains four review articles that describe advances in analysis of mutations responsible for the autoimmune lymphoproliferative syndrome (ALPS). This disease is triggered by a family of mutations in genes involved in the extrinsic apoptotic pathway such as FAS, FASL and CASP10. Advances in sequencing technology have enabled extended genetic testing of patients with various defects in alternative biological have pathways that can cause ALPS-like syndromes.

Neither B cell nor T cell - The unique group of innate lymphoid cells.

This special issue contains four review articles that analyze the development and biology of innate lymphoid cells (ILCs), which are the most recently-discovered group of innate immune cells. This unique group of lymphoid cells lacks the RAG gene and consequently does not express B cell nor T cell antigen-specific receptors. They are abundant at mucosal surfaces, where they play a role in immunity and homeostasis.

A small-molecule P2RX7 activator promotes anti-tumor immune responses and sensitizes lung tumor to immunotherapy.

Only a subpopulation of non-small cell lung cancer (NSCLC) patients responds to immunotherapies, highlighting the urgent need to develop therapeutic strategies to improve patient outcome. We develop a chemical positive modulator (HEI3090) of the purinergic P2RX7 receptor that potentiates αPD-1 treatment to effectively control the growth of lung tumors in transplantable and oncogene-induced mouse models and triggers long lasting antitumor immune responses. Mechanistically, the molecule stimulates dendritic P2RX7-expressing cells to generate IL-18 which leads to the production of IFN-γ by Natural Killer and CD4 T cells within tumors.

Evolutionary Origin of the P2X7 C-ter Region: Capture of an Ancient Ballast Domain by a P2X4-Like Gene in Ancient Jawed Vertebrates.

P2X purinergic receptors are extracellular ATP-gated ion channel receptors present on the cell plasma membrane. P2X receptors have been found in Metazoa, fungi, amoebas, and in plants. In mammals, P2X7 is expressed by a large number of cell types and is involved in inflammation and immunity.

Human Peripheral Blood Eosinophils Express High Levels of the Purinergic Receptor P2X4.

Extracellular nucleotides are important mediators of cell activation and trigger multiple responses via membrane receptors known as purinergic receptors (P2). P2X receptors are ligand-gated ion channels, activated by extracellular ATP. P2X4 is one of the most sensitive purinergic receptors, that is typically expressed by neurons, microglia, and some epithelial and endothelial cells.

Pleiotropic Roles of P2X7 in the Central Nervous System.

The purinergic receptor P2X7 is expressed in neural and immune cells known to be involved in neurological diseases. Its ligand, ATP, is a signaling molecule that can act as a neurotransmitter in physiological conditions or as a danger signal when released in high amount by damaged/dying cells or activated glial cells. Thus, ATP is a danger-associated molecular pattern.

New role of P2X7 receptor in an Alzheimer's disease mouse model.

Extracellular aggregates of amyloid β (Aβ) peptides, which are characteristic of Alzheimer's disease (AD), act as an essential trigger for glial cell activation and the release of ATP, leading to the stimulation of purinergic receptors, especially the P2X7 receptor (P2X7R). However, the involvement of P2X7R in the development of AD is still ill-defined regarding the dual properties of this receptor. Particularly, P2X7R activates the NLRP3 inflammasome leading to the release of the pro-inflammatory cytokine, IL-1β; however, P2X7R also induces cleavage of the amyloid precursor protein generating Aβ peptides or the neuroprotective fragment sAPPα.

Variations in Cellular Responses of Mouse T Cells to Adenosine-5'-Triphosphate Stimulation Do Not Depend on P2X7 Receptor Expression Levels but on Their Activation and Differentiation Stage.

A previous report has shown that regulatory T cells (Treg) were markedly more sensitive to adenosine-5'-triphosphate (ATP) than conventional T cells (Tconv). Another one has shown that Tregs and CD45RB Tconvs, but not CD45RB Tconvs, displayed similar high sensitivity to ATP. We have previously reported that CD45RB Tconvs expressing B220/CD45RABC molecules in a pre-apoptotic stage are resistant to ATP stimulation due to the loss of P2X7 receptor (P2X7R) membrane expression.

P2X4: A fast and sensitive purinergic receptor.

Extracellular nucleotides have been recognized as important mediators of activation, triggering multiple responses via plasma membrane receptors known as P2 receptors. P2 receptors comprise P2X ionotropic receptors and G protein-coupled P2Y receptors. P2X receptors are expressed in many tissues, where they are involved in a number of functions including synaptic transmission, muscle contraction, platelet aggregation, inflammation, macrophage activation, differentiation and proliferation, neuropathic and inflammatory pain.

P2X7 receptor promotes intestinal inflammation in chemically induced colitis and triggers death of mucosal regulatory T cells.

P2X7 receptor activation contributes to inflammation development in different pathologies. We previously reported that the P2X7 receptor is over-expressed in the gut mucosa of patients with inflammatory bowel disease, and that P2X7 inhibition protects against chemically induced colitis. Here, we investigated in detail the role of the P2X7 receptor in inflammatory bowel disease development, by treating P2X7 knockout (KO) and WT mice with two different (and established) colitis inductors.

Is the inflammasome relevant for epithelial cell function?

Inflammasomes are intracellular protein complexes that sense microbial components and damage of infected cells. Following activation by molecules released by pathogens or injured cells, inflammasomes activate caspase-1, allowing secretion of the pro-inflammatory cytokines IL-1β and IL-18 from innate immune cells. Inflammasomes are also expressed in epithelial cells, where their function has attracted less attention.

Reshaping procedures for the surgical management of corneal ectasia.

Unlabelled: Corneal ectasia is a progressive, degenerative, and noninflammatory thinning disorder of the cornea. Recently developed corneal reshaping techniques have expanded the treatment armamentarium available to the corneal specialist by offering effective nontransplant options. This review summarizes the current evidence base for corneal collagen crosslinking, topography-guided photorefractive keratectomy, and intrastromal corneal ring segment implantation for the treatment of corneal ectasia by analyzing the data published between the years 2000 and 2014.

Current knowledge about and recommendations for ocular methicillin-resistant Staphylococcus aureus.

Unlabelled: Staphylococcus aureus is the most important and common pathogen that infects patients following cataract surgery, laser in situ keratomileusis, and photorefractive keratectomy. It is reported to be the second most common pathogen causing bacterial keratitis around the world. Of special concern are increasing reports of postoperative methicillin-resistant S aureus (MRSA) infection.