ILC2s: New Actors in Tumor Immunity

Innate lymphoid cells (ILCs) represent the most recently identified family of innate lymphocytes that act as first responders, maintaining tissue homeostasis and protecting epithelial barriers. In the last few years, group 2 ILCs (ILC2s) have emerged as key regulators in several immunological processes such as asthma and allergy. Whilst ILC2s are currently being evaluated as novel targets for immunotherapy in these diseases, their involvement in tumor immunity has only recently begun to be deciphered. Here, we provide a comprehensive overview of the pleiotropic roles of ILC2s in different tumor settings. Furthermore, we discuss how different therapeutic approaches targeting ILC2s could improve the efficacy of current tumor immunotherapies

The salivary microbiome for differentiating individuals: proof of principle.

Human identification has played a prominent role in forensic science for the past two decades. Identification based on unique genetic traits is driving the field. However, this may have limitations, for instance, for twins. Moreover, high-throughput sequencing techniques are now available and may provide a high amount of data likely useful in forensic science. This study investigates the potential for bacteria found in the salivary microbiome to be used to differentiate individuals. Two different targets (16S rRNA and rpoB) were chosen to maximise coverage of the salivary microbiome and when combined, they increase the power of differentiation (identification). Paired-end Illumina high-throughput sequencing was used to analyse the bacterial composition of saliva from two different people at four different time points (t = 0 and t = 28 days and then one year later at t = 0 and t = 28 days). Five major phyla dominate the samples: Firmicutes, Proteobacteria, Actinobacteria, Bacteroidetes and Fusobacteria. Streptococcus, a Firmicutes, is one of the most abundant aerobic genera found in saliva and targeting Streptococcus rpoB has enabled a deeper characterisation of the different streptococci species, which cannot be differentiated using 16S rRNA alone. We have observed that samples from the same person group together regardless of time of sampling. The results indicate that it is possible to distinguish two people using the bacterial microbiota present in their saliva

A software processing chain for evaluating thesaurus quality

Thesauri are knowledge models commonly used for information classification and retrieval whose structure is defined by standards that describe the main features the concepts and relations must have. However, following these standards requires a deep knowledge of the field the thesaurus is going to cover and experience in their creation. To help in this task, this paper describes a software processing chain that provides different validation components that evaluates the quality of the main thesaurus features

Healthy and patient type 2 innate lymphoid cells are differently affected by in vitro culture conditions

Background: Type 2 innate lymphoid cells (ILC2s) have emerged as key players in the development of type 2 driven diseases such as allergy and asthma. Due to their low number in the circulation, in vitro expansion is needed to unravel their mechanisms of action. Purpose: The aim of this study is to assess the impact of different culture conditions and address whether the method of expansion may distinctly affect healthy donor or patient-derived ILC2s. Methods: Here, we described the impact of six different culture conditions on the proliferation, phenotype and function of human ILC2s freshly obtained from healthy donors (healthy ILC2s) and allergic patients (patient ILC2s). Results: We showed that the cytokine cocktail or the PHA induced the highest proliferation of healthy ILC2s and patient ILC2s, respectively. We observed that the stromal cells OP9, used as ILC2 feeders, did not boost their proliferation, but impaired the activation marker expression and the function of patient ILC2s. Furthermore, we demonstrated that the culture conditions differently impacted the activation state of c-Kithigh and c-Kitlow ILC2s, in both healthy donors and allergic patients. Last, we also observed that ILC2s expanded only with IL-2 and IL-7 were the most prone to secrete IL-5 and IL-13 upon IL-33 stimulation. In contrast, in patients, the addition of OP9 cells during the expansion restrained their type 2 cytokine secretory functions. Conclusion: This report highlights that culture conditions distinctly impacted on the healthy or patient ILC2 behavior, with important consequences for their study in disease settings

Towards a typology of spatial relations and properties for urban applications

Relations that occur between features located in space–like the fact that a street is surrounded by very high buildings, that an airport is close to a city- as well as spatial properties of features–like the height and width of a door- play an important role for many urban applications. Digital models of cities can assist in the evaluation of these relations and properties either through visualisation or through computation, mainly based on geometrical information. Hence, considering the objective of explaining to potential users of these city models what useful information they can derive from these data and how, a possible way to address this objective lies in the usage of a pivot model composed of relevant spatial properties and relations, connected to information meaningful to the user and connected to the possible computation of them on available data. This paper firstly sets the ground for a typology of such relevant relations and properties that are shared by different applications and that can be derived/approximated from existing data. It then proposes a model to describe these properties and relations and connect them to their possible computation based on data (2D or 3D). An important aspect of this model is to distinguish between a conceptual layer where relations occur between “real world” features and an implementation layer where they are calculated based on database features and geometries

c-Maf enforces cytokine production and promotes memory-like responses in mouse and human type 2 innate lymphoid cells

Group-2 innate lymphoid cells (ILC2s), which are involved in type 2 inflammatory diseases such as allergy, can exhibit immunological memory, but the basis of this ILC2 "trained immunity" has remained unclear. Here, we found that stimulation with IL-33/IL-25 or exposure to the allergen papain induces the expression of the transcription factor c-Maf in mouse ILC2s. Chronic papain exposure results in high production of IL-5 and IL-13 cytokines and lung eosinophil recruitment, effects that are blocked by c-Maf deletion in ILCs. Transcriptomic analysis revealed that knockdown of c-Maf in ILC2s suppresses expression of type 2 cytokine genes, as well as of genes linked to a memory-like phenotype. Consistently, c-Maf was found highly expressed in human adult ILC2s but absent in cord blood and required for cytokine production in isolated human ILC2s. Furthermore, c-Maf-deficient mouse or human ILC2s failed to exhibit strengthened (“trained”) responses upon repeated challenge. Thus, the expression of c-Maf is indispensable for optimal type 2 cytokine production and proper memory-like responses in group-2 innate lymphoid cells

3D City Models and urban information: Current issues and perspectives

Considering sustainable development of cities implies investigating cities in a holistic way taking into account many interrelations between various urban or environmental issues. 3D city models are increasingly used in different cities and countries for an intended wide range of applications beyond mere visualization. Could these 3D City models be used to integrate urban and environmental knowledge? How could they be improved to fulfill such role? We believe that enriching the semantics of current 3D city models, would extend their functionality and usability; therefore, they could serve as integration platforms of the knowledge related to urban and environmental issues allowing a huge and significant improvement of city sustainable management and development. But which elements need to be added to 3D city models? What are the most efficient ways to realize such improvement / enrichment? How to evaluate the usability of these improved 3D city models? These were the questions tackled by the COST Action TU0801 “Semantic enrichment of 3D city models for sustainable urban development”. This book gathers various materials developed all along the four year of the Action and the significant breakthroughs

PeroxiBase: a database with new tools for peroxidase family classification

Peroxidases (EC 1.11.1.x), which are encoded by small or large multigenic families, are involved in several important physiological and developmental processes. They use various peroxides as electron acceptors to catalyse a number of oxidative reactions and are present in almost all living organisms. We have created a peroxidase database (http://peroxibase.isb-sib.ch) that contains all identified peroxidase-encoding sequences (about 6000 sequences in 940 organisms). They are distributed between 11 superfamilies and about 60 subfamilies. All the sequences have been individually annotated and checked. PeroxiBase can be consulted using six major interlink sections ‘Classes’, ‘Organisms’, ‘Cellular localisations’, ‘Inducers’, ‘Repressors’ and ‘Tissue types’. General documentation on peroxidases and PeroxiBase is accessible in the ‘Documents’ section containing ‘Introduction’, ‘Class description’, ‘Publications’ and ‘Links’. In addition to the database, we have developed a tool to classify peroxidases based on the PROSITE profile methodology. To improve their specificity and to prevent overlaps between closely related subfamilies the profiles were built using a new strategy based on the silencing of residues. This new profile construction method and its discriminatory capacity have been tested and validated using the different peroxidase families and subfamilies present in the database. The peroxidase classification tool called PeroxiScan is accessible at the following address: http://peroxibase.isb-sib.ch/peroxiscan.php

Impact of clinical pharmacy on the psychotropic drugs prescription in neurological rehabilitation: A retrospective study

IntroductionPsychotropic drugs are frequently prescribed in neuro-rehabilitation. In our institution, they account for 18% of prescriptions. For several years, clinical pharmacy activities were developed in collaboration with physicians and psychiatrists. The aim of this study is to evaluate the impact of this approach by the retrospective measure of psychotropic drugs consumption over 4 years, and link them to the evolution of hospital stays recorded through the PMSI (Programme de médicalisation des systèmes d’information, France).MethodsThe study took place over the period 2010–2013. It included three steps: 1/Monitoring of psychotropic drugs consumption (antipsychotics, anxiolytics, hypnotics and antidepressants) of 9 units (225 beds), by value and treatment days calculated from the daily average dosage (THERIAQUE); 2/Identification of hospitalised patients with at least one diagnosis code of either depression, anxiety, insomnia, and/or psychotic disorders; 3/Analysis of patient data with regard to drug consumption.ResultsFrom 2010 to 2013, the cost of psychotropic drugs was reduced by 24%, from 17,617 to 13,366 euros. The number of treatment days decreased by 30% from 84,765 to 59,466 days. The most significant decline was for hypnotic drugs (–62%) (28,110 to 10,623 days), and anxiolytic drugs (–37%) (28,958 to 18,343 days). The usage of antidepressant drugs increased by 21% (19,996 to 24,154 days), while the usage of antipsychotic drugs was stable (6346 days in 2013). During the same period, the overall number of patients with psychological diagnosis code hospital stays increased by 146% (213 to 523). It can be further detailed as follows: +380% for patients with an anxiety disorder (60 to 287), +71% for patients with depressive symptoms (78 to 133). Stays of patients with psychotic disorders remained stable.DiscussionThis study illustrates that a clinical pharmacy action targeted on psychotropic drugs prescriptions in collaboration with physicians and psychiatrists has reduced their consumption in neuro-rehabilitation. This decrease concerns mainly anxiolytic drugs and hypnotic drugs, despite the rise in number of hospital stays of patients with anxiety disorders. These results follow the recent recommendations of the ANSM (Agence nationale de sécurité du médicament, France)