Mapping Rora expression in resting and activated CD4+ T cells.

The transcription factor Rora has been shown to be important for the development of ILC2 and the regulation of ILC3, macrophages and Treg cells. Here we investigate the role of Rora across CD4+ T cells in general, but with an emphasis on Th2 cells, both in vitro as well as in the context of several in vivo type 2 infection models. We dissect the function of Rora using overexpression and a CD4-conditional Rora-knockout mouse, as well as a RORA-reporter mouse. We establish the importance of Rora in CD4+ T cells for controlling lung inflammation induced by Nippostrongylus brasiliensis infection, and have measured the effect on downstream genes using RNA-seq. Using a systematic stimulation screen of CD4+ T cells, coupled with RNA-seq, we identify upstream regulators of Rora, most importantly IL-33 and CCL7. Our data suggest that Rora is a negative regulator of the immune system, possibly through several downstream pathways, and is under control of the local microenvironment

Erratum to: Single cell analysis of CD4+ T cell differentiation reveals three major cell states and progressive acceleration of proliferation.

Background: Differentiation of lymphocytes is frequently accompanied by cell cycle changes, interplay that is of central importance for immunity but is still incompletely understood. Here, we interrogate and quantitatively model how proliferation is linked to differentiation in CD4+ T cells. Results: We perform ex vivo single-cell RNA-sequencing of CD4+ T cells during a mouse model of infection that elicits a type 2 immune response and infer that the differentiated, cytokine-producing cells cycle faster than early activated precursor cells. To dissect this phenomenon quantitatively, we determine expression profiles across consecutive generations of differentiated and undifferentiated cells during Th2 polarization in vitro. We predict three discrete cell states, which we verify by single-cell quantitative PCR. Based on these three states, we extract rates of death, division and differentiation with a branching state Markov model to describe the cell population dynamics. From this multi-scale modelling, we infer a significant acceleration in proliferation from the intermediate activated cell state to the mature cytokine-secreting effector state. We confirm this acceleration both by live imaging of single Th2 cells and in an ex vivo Th1 malaria model by single-cell RNA-sequencing. Conclusion: The link between cytokine secretion and proliferation rate holds both in Th1 and Th2 cells in vivo and in vitro, indicating that this is likely a general phenomenon in adaptive immunity

T cell fate and clonality inference from single-cell transcriptomes.

We developed TraCeR, a computational method to reconstruct full-length, paired T cell receptor (TCR) sequences from T lymphocyte single-cell RNA sequence data. TraCeR links T cell specificity with functional response by revealing clonal relationships between cells alongside their transcriptional profiles. We found that T cell clonotypes in a mouse Salmonella infection model span early activated CD4(+) T cells as well as mature effector and memory cells

Gene expression variability across cells and species shapes innate immunity.

As the first line of defence against pathogens, cells mount an innate immune response, which varies widely from cell to cell. The response must be potent but carefully controlled to avoid self-damage. How these constraints have shaped the evolution of innate immunity remains poorly understood. Here we characterize the innate immune response's transcriptional divergence between species and variability in expression among cells. Using bulk and single-cell transcriptomics in fibroblasts and mononuclear phagocytes from different species, challenged with immune stimuli, we map the architecture of the innate immune response. Transcriptionally diverging genes, including those that encode cytokines and chemokines, vary across cells and have distinct promoter structures. Conversely, genes that are involved in the regulation of this response, such as those that encode transcription factors and kinases, are conserved between species and display low cell-to-cell variability in expression. We suggest that this expression pattern, which is observed across species and conditions, has evolved as a mechanism for fine-tuned regulation to achieve an effective but balanced response

Culture and Education as Cornerstones of EU-INDIA International Relations: the case of the E-QUAL project

This article is intended to present the \u201cE-QUAL - Enhancing Quality, Access and Governance of Undergraduate Education in India\u201d project, explaining why the European Union funded it and with which aim. It will consider how so-called cultural diplomacy plays a key role in EU-India international relations. EU international cultural relations are shaped to make the EU a stronger global actor and to connect international partners at a deeper level, involving key civil society actors such as Universities. The EU has developed a comprehensive approach and a series of tools to finance education actions. Among these was the "Support to Indo-European Interactions on Higher Education\u201d programme which funded the E-QUAL project from 2013 to 2017. The E-QUAL project aimed to create an innovative approach to enhance the quality, access to and governance of undergraduate education in India, which was going through a phase of acute crisis due to a mismatch between quality and quantity/numbers. The project\u2019s impact is in line with the EU-India policy cooperation, and dialogue developed especially in the framework of EU-India partnership instruments, covering sectoral cooperation and contacts between people at various levels and in several areas, including higher education

Taking cover before the outbreak: understanding precautionary behaviors of Chinese in Italy in the COVID-19 scenario

This paper provides an empirical exploration of the preemptive measures adopted by Chinese in Italy vis-à-vis the early outbreak of COVID-19. Based on a quantitative dataset obtained through an online survey, the assessment of preemptive self-isolation has been pursued in relation to: the sources of information regarding the pandemic, the perception of risk, the level of trust towards both Italian and Chinese authorities, and the level of perceived stigma. According to the evidences we have collected, most of the Chinese living in Italy began an “all-out self-isolation” prior to the enforcement of the national lockdown. Such behaviors appear as the result of individual decisions taken on the basis of an individual, high perception of risk, apprised by Chinese sources of information and fueled by distrust towards policies enforced by the Italian governmental authorities. This article suggests that the precautionary behaviors of the Chinese in Italy can be seen as the result of the combination of their “preparedness” and their perception of stigma and discrimination