Integrin α2β1 regulates collagen I tethering to modulate hyperresponsiveness in reactive airway disease models.

Severe asthma remains challenging to manage and has limited treatment options. We have previously shown that targeting smooth muscle integrin α5β1 interaction with fibronectin can mitigate the effects of airway hyperresponsiveness by impairing force transmission. In this study, we show that another member of the integrin superfamily, integrin α2β1, is present in airway smooth muscle and capable of regulating force transmission via cellular tethering to the matrix protein collagen I and, to a lesser degree, laminin-111.

The Eph-related tyrosine kinase ligand Ephrin-B1 marks germinal center and memory precursor B cells.

Identification of germinal center (GC) B cells is typically reliant on the use of surface activation markers that exhibit a wide range of expression. Here, we identify Ephrin-B1, a ligand for Eph-related receptor tyrosine kinases, as a specific marker of mature GC B cells. The number of Ephrin-B1 GC B cells increases during the course of an immune response with Ephrin-B1 GC B cells displaying elevated levels of Bcl6, , and relative to their Ephrin-B1 counterparts.

Regulation of B cell fate by chronic activity of the IgE B cell receptor.

IgE can trigger potent allergic responses, yet the mechanisms regulating IgE production are poorly understood. Here we reveal that IgE B cells are constrained by chronic activity of the IgE B cell receptor (BCR). In the absence of cognate antigen, the IgE BCR promoted terminal differentiation of B cells into plasma cells (PCs) under cell culture conditions mimicking T cell help.

Determination of key structure-activity relationships in siRNA delivery with a mixed micelle system.

Short interfering ribonucleic acids (siRNAs) offer a highly specific and selective form of therapy for diseases with a genetic component; however the poor pharmacokinetic properties of the molecule have impeded its development into a therapeutic for use in vivo. Several different approaches have been taken to develop a successful siRNA delivery system but these systems lack the flexibility for easy optimisation. Here, we propose a polymeric nanoparticle (PNP) system consisting of two amphiphilic diblock copolymers which allow for the rapid determination of structure-activity relationships involving gene knockdown and toxicity.

Self-reported oral health status of adults resident in Medway, Kent in 2009.

Aim: In order to assess the oral health status, oral behaviours and use of oral healthcare services of the adult population of Medway (Kent) in 2009, NHS Medway commissioned an assessment. Its aims were to understand oral health and impacts, behaviours and the use of dental services in order to inform future development of dental services.

Methods: A self-reported postal questionnaire survey using relevant questions from the 1998 national Adult Dental Health Survey (ADHS) was performed.

MicroRNA-29 regulates T-box transcription factors and interferon-γ production in helper T cells.

MicroRNA (miRNA)-deficient helper T cells exhibit abnormal IFN-γ production and decreased proliferation. However, the contributions of individual miRNAs to this phenotype remain poorly understood. We conducted a screen for miRNA function in primary T cells and identified individual miRNAs that rescue the defects associated with miRNA deficiency.

The sphingosine 1-phosphate receptor S1P₂ maintains the homeostasis of germinal center B cells and promotes niche confinement.

Mice deficient in sphingosine 1-phosphate receptor type 2 (S1P(2)) develop diffuse large B cell lymphoma. However, the role of S1P(2) in normal germinal center (GC) physiology is unknown. Here we show that S1P(2)-deficient GC B cells outgrew their wild-type counterparts in chronically established GCs.

B cells within germinal centers migrate preferentially from dark to light zone.

One of the main questions in the field of imaging immune cell migration in living tissues is whether cells fulfill their functionality via random or nonrandom migration processes. For some applications, this issue has remained controversial even after publication of various imaging studies. A prime example is B-cell migration in germinal centers (GCs) where somatic hypermutation and clonal selection of B cells are thought to occur within morphologically distinct regions termed dark zone (DZ) and light zone (LZ).

Genetic analysis of basophil function in vivo.

Contributions by basophils to allergic and helminth immunity remain incompletely defined. Using sensitive interleukin 4 (Il4) reporter alleles, we demonstrate here that basophil IL-4 production occurs by a CD4(+) T cell-dependent process restricted to the peripheral tissues affected. We genetically marked and achieved specific deletion of basophils and found that basophils did not mediate T helper type 2 (T(H)2) priming in vivo.

Follicular dendritic cell networks of primary follicles and germinal centers: phenotype and function.

Follicular dendritic cells (FDCs) were identified decades ago by their ability to retain immune complexes and more recent findings indicate that they are a source of B cell attractants and trophic factors. New imaging studies have shown that B cells closely associate with their dendritic processes during migration. Here we will review the properties of these specialized follicular stromal cells and provide an update on the requirements for their maturation into phenotypically distinct cells within germinal center light and dark zones.

Role of CXCR5 and CCR7 in follicular Th cell positioning and appearance of a programmed cell death gene-1high germinal center-associated subpopulation.

Th cell access to primary B cell follicles is dependent on CXCR5. However, whether CXCR5 induction on T cells is sufficient in determining their follicular positioning has been unclear. In this study, we find that transgenic CXCR5 overexpression is not sufficient to promote follicular entry of naive T cells unless the counterbalancing influence of CCR7 ligands is removed.

Germinal-center organization and cellular dynamics.

Germinal centers (GCs) are important sites of antibody affinity maturation. In the classical model, the GC dark zone contains large centroblasts that are rapidly proliferating and undergoing somatic hypermutation of their antibody variable-region genes. Centroblasts give rise to smaller nonproliferating centrocytes in the light zone that compete for binding antigen on follicular dendritic cells.

Imaging of germinal center selection events during affinity maturation.

The germinal center (GC) is an important site for the generation and selection of B cells bearing high-affinity antibodies, yet GC cell migration and interaction dynamics have not been directly observed. Using two-photon microscopy of mouse lymph nodes, we revealed that GC B cells are highly motile and extend long cell processes. They transited between GC dark and light zones and divided in both regions, although these B cells resided for only several hours in the light zone where antigen is displayed.

TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis.

T cell immunoglobulin-domain and mucin-domain (TIM) proteins constitute a receptor family that was identified first on kidney and liver cells; recently it was also shown to be expressed on T cells. TIM-1 and -3 receptors denote different subsets of T cells and have distinct regulatory effects on T cell function. Ferritin is a spherical protein complex that is formed by 24 subunits of H- and L-ferritin.

Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5.

Germinal center (GC) dark and light zones segregate cells undergoing somatic hypermutation and antigen-driven selection, respectively, yet the factors guiding this organization are unknown. We report here that GC organization was absent from mice deficient in the chemokine receptor CXCR4. Centroblasts had high expression of CXCR4 and GC B cells migrated toward the CXCR4 ligand SDF-1 (CXCL12), which was more abundant in the dark zone than in the light zone.

Recruitment and retention of dental nurses and dental hygienists in general practice.

Purpose Of Study: To explore the recruitment and retention of dental nurses and dental hygienists working in general dental practice in West Kent, and to identify training needs.

Basic Procedure: Questionnaire survey of 195 general dental practices in West Kent.

Main Findings: Problems with turnover of staff were reported by 19% of practices.