Patients at Risk for Transfusion-A Six-Year Multicentre Analysis of More Than 320,000 Helicopter Emergency Medical Service Missions.

Background: In Europe, ambulances are increasingly being equipped with blood products for prehospital use. Available evidence on the early administration of blood products comes from military medicine and the Anglo-American medical literature; the evidence cannot be easily transferred to European countries.

Objectives: This study assesses the incidence of patients with massive haemorrhage after trauma and the potential need for prehospital blood transfusions.

Vascular miR-181b controls tissue factor-dependent thrombogenicity and inflammation in type 2 diabetes.

Background: Diabetes mellitus is characterized by chronic vascular inflammation leading to pathological expression of the thrombogenic full length (fl) tissue factor (TF) and its isoform alternatively-spliced (as) TF. Blood-borne TF promotes factor (F) Xa generation resulting in a pro-thrombotic state and cardiovascular complications. MicroRNA (miR)s impact gene expression on the post-transcriptional level and contribute to vascular homeostasis.

Annual severity increment score as a tool for stratifying patients with Niemann-Pick disease type C and for recruitment to clinical trials.

Background: Niemann-Pick disease type C (NPC) is a lysosomal storage disease with a heterogeneous neurodegenerative clinical course. Multiple therapies are in clinical trials and inclusion criteria are currently mainly based on age and neurological signs, not taking into consideration differential individual rates of disease progression.

Results: In this study, we have evaluated a simple metric, denoted annual severity increment score (ASIS), that measures rate of disease progression and could easily be used in clinical practice.

Eosinophil depletion suppresses radiation-induced small intestinal fibrosis.

Radiation-induced intestinal fibrosis (RIF) is a serious complication after abdominal radiotherapy for pelvic tumor or peritoneal metastasis. Herein, we show that RIF is mediated by eosinophil interactions with α-smooth muscle actin-positive (α-SMA) stromal cells. Abdominal irradiation caused RIF especially in the submucosa (SM) of the small intestine, which was associated with the excessive accumulation of eosinophils in both human and mouse.

A catch-22: Interleukin-22 and cancer.

Barrier surfaces of multicellular organisms are in constant contact with the environment and infractions to the integrity of epithelial surfaces is likely a frequent event. Interestingly, components of the immune system, that can be activated by environmental compounds such as the microbiota or nutrients, are interspersed among epithelial cells or directly underlie the epithelium. It is now appreciated that immune cells continuously receive and integrate signals from the environment.

Recipe for IBD: can we use food to control inflammatory bowel disease?

The mucosal immune system and the microbiota in the intestinal tract have recently been shown to play a key role in the pathogenesis of inflammatory bowel disease (IBD). Both of these can be influenced by food. Thus, we propose dietary intervention as a therapeutic option for IBD.

NKp30 isoforms and NKp30 ligands are predictive biomarkers of response to imatinib mesylate in metastatic GIST patients.

Despite effective targeted therapy acting on and tyrosine kinases, gastrointestinal stromal tumors (GIST) escape treatment by acquiring mutations conveying resistance to imatinib mesylate (IM). Following the identification of NKp30-based immunosurveillance of GIST and the off-target effects of IM on NK cell functions, we investigated the predictive value of NKp30 isoforms and NKp30 soluble ligands in blood for the clinical response to IM. The relative expression and the proportions of NKp30 isoforms markedly impacted both event-free and overall survival, in two independent cohorts of metastatic GIST.

An essential role for the IL-2 receptor in T cell function.

Regulatory T cells (T cells), which have abundant expression of the interleukin 2 receptor (IL-2R), are reliant on IL-2 produced by activated T cells. This feature indicates a key role for a simple network based on the consumption of IL-2 by T cells in their suppressor function. However, congenital deficiency in IL-2R results in reduced expression of the T cell lineage-specification factor Foxp3, which has confounded experimental efforts to understand the role of IL-2R expression and signaling in the suppressor function of T cells.

Fibrosis is not just fibrosis - basement membrane modelling and collagen metabolism differs between hepatitis B- and C-induced injury.

Background: While morphological patterns differ, the molecular phenotype of liver fibrosis is considered a stereotypical response to chronic liver injury. However, with different cellular triggers and networks regulating fibrosis, the molecular responses of the injured liver may not be identical.

Aim: To investigate whether differences in extracellular matrix (ECM) composition of the liver during fibrogenesis in two seemingly similar types of viral hepatitis could be reflected by differences in ECM turnover.

Micro-RNA-126 Reduces the Blood Thrombogenicity in Diabetes Mellitus via Targeting of Tissue Factor.

Objective: Diabetes mellitus involves vascular inflammatory processes and is a main contributor to cardiovascular mortality. Notably, heightened levels of circulating tissue factor (TF) account for the increased thrombogenicity and put those patients at risk for thromboembolic events. Here, we sought to investigate the role of micro-RNA (miR)-driven TF expression and thrombogenicity in diabetes mellitus.

Parallels and differences between innate and adaptive lymphocytes.

Lymphocytes are essential in innate and adaptive immunity. Recent insights suggest that some innate lymphocytes execute functions with adaptive characteristics, while adaptive lymphocytes can operate in ways reminiscent of innate cells. Rather than partitioning lymphocytes according to the type of effector function they execute, we propose that a relevant discrimination relates to the existence of conventional T cells in a naive state.

Tissue residency of innate lymphoid cells in lymphoid and nonlymphoid organs.

Innate lymphoid cells (ILCs) contribute to barrier immunity, tissue homeostasis, and immune regulation at various anatomical sites throughout the body. How ILCs maintain their presence in lymphoid and peripheral tissues thus far has been unclear. We found that in the lymphoid and nonlymphoid organs of adult mice, ILCs are tissue-resident cells that were maintained and expanded locally under physiologic conditions, upon systemic perturbation of immune homeostasis and during acute helminth infection.

Interleukin-12 and -23 Control Plasticity of CD127(+) Group 1 and Group 3 Innate Lymphoid Cells in the Intestinal Lamina Propria.

Human group 1 ILCs consist of at least three phenotypically distinct subsets, including NK cells, CD127(+) ILC1, and intraepithelial CD103(+) ILC1. In inflamed intestinal tissues from Crohn's disease patients, numbers of CD127(+) ILC1 increased at the cost of ILC3. Here we found that differentiation of ILC3 to CD127(+) ILC1 is reversible in vitro and in vivo.

Host microbiota constantly control maturation and function of microglia in the CNS.

As the tissue macrophages of the CNS, microglia are critically involved in diseases of the CNS. However, it remains unknown what controls their maturation and activation under homeostatic conditions. We observed substantial contributions of the host microbiota to microglia homeostasis, as germ-free (GF) mice displayed global defects in microglia with altered cell proportions and an immature phenotype, leading to impaired innate immune responses.

Interferon-λ and interleukin 22 act synergistically for the induction of interferon-stimulated genes and control of rotavirus infection.

The epithelium is the main entry point for many viruses, but the processes that protect barrier surfaces against viral infections are incompletely understood. Here we identified interleukin 22 (IL-22) produced by innate lymphoid cell group 3 (ILC3) as an amplifier of signaling via interferon-λ (IFN-λ), a synergism needed to curtail the replication of rotavirus, the leading cause of childhood gastroenteritis. Cooperation between the receptor for IL-22 and the receptor for IFN-λ, both of which were 'preferentially' expressed by intestinal epithelial cells (IECs), was required for optimal activation of the transcription factor STAT1 and expression of interferon-stimulated genes (ISGs).

Leukocyte-derived IFN-α/β and epithelial IFN-λ constitute a compartmentalized mucosal defense system that restricts enteric virus infections.

Epithelial cells are a major port of entry for many viruses, but the molecular networks which protect barrier surfaces against viral infections are incompletely understood. Viral infections induce simultaneous production of type I (IFN-α/β) and type III (IFN-λ) interferons. All nucleated cells are believed to respond to IFN-α/β, whereas IFN-λ responses are largely confined to epithelial cells.

Adipose tissue: ILC2 crank up the heat.

White-to-beige conversion of adipocytes is one of the most promising approaches to therapeutically target obesity; however, the signals driving this process had largely remained unclear. Recently, two publications, Brestoff et al. (2014) in Nature and Lee et al.

Development, differentiation, and diversity of innate lymphoid cells.

Recent years have witnessed the discovery of an unprecedented complexity in innate lymphocyte lineages, now collectively referred to as innate lymphoid cells (ILCs). ILCs are preferentially located at barrier surfaces and are important for protection against pathogens and for the maintenance of organ homeostasis. Inappropriate activation of ILCs has been linked to the pathogenesis of inflammatory and autoimmune disorders.

Interactions between innate and adaptive lymphocytes.

Innate lymphocytes - including natural killer cells and the recently discovered innate lymphoid cells - have crucial roles during infection, tissue injury and inflammation. Innate signals regulate the activation and homeostasis of innate lymphocytes. The contribution of the adaptive immune system to the coordination of innate lymphocyte responses is less well understood.

Transcription factors controlling innate lymphoid cell fate decisions.

The mucosal epithelium is in direct contact with symbiotic and pathogenic microorganisms. Therefore, the mucosal surface is the principal portal of entry for invading pathogens and immune cells accumulated in the intestine to prevent infections. In addition to these conventional immune system functions, it has become clear that immune cells during steady-state continuously integrate microbial and nutrient-derived signals from the environment to support organ homeostasis.