Regulatory T Cells GATA Have It

The factors that control regulatory T (Treg) cell homeostasis and function are still being defined. In this issue of Immunity, Wang et al. (2011) demonstrate that the Th2 cell-associated transcription factor GATA-3 helps control Foxp3 expression in Treg cells and is required for their proper functional activity in vivo

Genome-wide mapping reveals single-origin chromosome replication in Leishmania, a eukaryotic microbe

Background DNA replication initiates on defined genome sites, termed origins. Origin usage appears to follow common rules in the eukaryotic organisms examined to date: all chromosomes are replicated from multiple origins, which display variations in firing efficiency and are selected from a larger pool of potential origins. To ask if these features of DNA replication are true of all eukaryotes, we describe genome-wide origin mapping in the parasite Leishmania. Results Origin mapping in Leishmania suggests a striking divergence in origin usage relative to characterized eukaryotes, since each chromosome appears to be replicated from a single origin. By comparing two species of Leishmania, we find evidence that such origin singularity is maintained in the face of chromosome fusion or fission events during evolution. Mapping Leishmania origins suggests that all origins fire with equal efficiency, and that the genomic sites occupied by origins differ from related non-origins sites. Finally, we provide evidence that origin location in Leishmania displays striking conservation with Trypanosoma brucei, despite the latter parasite replicating its chromosomes from multiple, variable strength origins. Conclusions The demonstration of chromosome replication for a single origin in Leishmania, a microbial eukaryote, has implications for the evolution of origin multiplicity and associated controls, and may explain the pervasive aneuploidy that characterizes Leishmania chromosome architecture

Insulin signaling as a therapeutic mechanism of lithium in bipolar disorder

In this paper, we propose that lithium may exert its therapeutic effect in bipolar disorder by acting on insulin signaling pathways. Specifically, we assess the importance of the phosphatidylinositol 3-kinase/Protein Kinase B (PI3K/Akt) insulin signaling pathway and we assess how the action of lithium on both glycogen synthase kinase-3 (GSK3) and the phosphatidylinositol cycle may lead to mood stabilization mediated by PI3K/Akt insulin signaling. We also highlight evidence that several other actions of lithium (including effects on Akt, Protein kinase C (PKC), and sodium myo-inositol transporters) are putative mediators of insulin signaling. This novel mode of action of lithium is consistent with an emerging consensus that energy dysregulation represents a core deficit in bipolar disorder. It may also provide context for the significant co-morbidity between bipolar disorder, type 2 diabetes, and other forms of metabolic illness characterized by impaired glucose metabolism. It is suggested that developments in assessing neuronal insulin signaling using extracellular vesicles would allow for this hypothesis to be tested in bipolar disorder patients

Setting up new chemical engineering degree programmes: Exercises in design and retrofit within constraints

The rise in popularity of chemical engineering among students entering university has prompted expansion of the UK provision, through increased intake into current degree programmes and with the rise of new providers. The former entails logistical challenges of processing larger numbers through existing infrastructures whilst maintaining the student experience. The latter entails challenges of designing and introducing programmes that build harmoniously on existing non-chemical engineering provision, within the constraints of university validation procedures and physical resources, and in the face of uncertainty around student and staff recruitment, while aspiring to implement best practice in chemical engineering content and pedagogy. Following a review of the UK chemical engineering landscape and a critique of literature guidance on the appropriate content of chemical engineering curricula, this paper illustrates the issues of new programme development through the approaches and experiences of a new provider, the University of Huddersfield, which introduced new chemical engineering programmes from academic year 2013-14. The paper addresses specifying the content of chemical engineering programmes to align with accreditation requirements and literature advice while maintaining distinctiveness. The constraints imposed by the need to specify and validate courses internally and to minimise substantive programme changes subsequently, whilst responding to the opportunities that arise as staff are recruited and to external developments and unplanned incidents, are highlighted and illustrated, in order to draw lessons that might help to guide other new entrants

Living in Peace: Host-Microbiota Mutualism in the Skin

Commensal microbes colonize the skin where they promote immune development and prevent infection without inducing damaging inflammatory responses. In this issue of Cell Host & Microbe, Scharschmidt et al. (2017) show that during hair follicle development, commensals induce regulatory T cell migration to the skin to ensure cutaneous homeostasis

Rapid Acquisition of Tissue-specific Homing Phenotypes by CD4+ T Cells Activated in Cutaneous or Mucosal Lymphoid Tissues

Effector and memory T cells can be subdivided based on their ability to traffic through peripheral tissues such as inflamed skin and intestinal lamina propria, a property controlled by expression of ‘tissue-specific’ adhesion and chemoattractant receptors. However, little is known about the development of these selectively homing T cell subsets, and it is unclear whether activation in cutaneous versus intestinal lymphoid organs directly results in effector/memory T cells that differentially express adhesion and chemoattracant receptors targeting them to the corresponding nonlymphoid site. We define two murine CD4+ effector/memory T cell subsets that preferentially localize in cutaneous or intestinal lymphoid organs by their reciprocal expression of the adhesion molecules P-selectin ligand (P-lig) and α4β7, respectively. We show that within 2 d of systemic immunization CD4+ T cells activated in cutaneous lymph nodes upregulate P-lig, and downregulate α4β7, while those responding to antigen in intestinal lymph nodes selectively express high levels of α4β7 and acquire responsiveness to the intestinal chemokine thymus-expressed chemokine (TECK). Thus, during an immune response, local microenvironments within cutaneous and intestinal secondary lymphoid organs differentially direct T cell expression of these adhesion and chemoattractant receptors, targeting the resulting effector T cells to the inflamed skin or intestinal lamina propria

In vivo sites and cellular mechanisms of T reg cell–mediated suppression

Regulatory CD4 T (T reg) cells control immune responses to self-antigens and pathogens. However, where T reg cells act to curtail effector T cells in vivo and what stage of effector T cell activation or differentiation is targeted by T reg cells remain unknown. Furthermore, a requirement for direct effector T cell–T reg cell contact in vivo has not been ascertained. Varying answers to these important questions have been provided by several new studies