David J Cousins

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Asthma and chronic obstructive pulmonary disease (COPD) are associated with Th2 and Th1 differentiated T cells. The cytokine thymic stromal lymphopoietin (TSLP) promotes differentiation of Th2 T cells and secretion of chemokines which preferentially attract them. We hypothesized that there is distinct airways expression of TSLP and chemokines which(More)
Phenotypic modulation of airway smooth muscle (ASM) is an important feature of airway remodeling in asthma that is characterized by enhanced proliferation and secretion of pro-inflammatory chemokines. These activities are regulated by the concentration of free Ca(2+) in the cytosol ([Ca(2+)](i)). A rise in [Ca(2+)](i) is normalized by rapid reuptake of(More)
Signaling through the TLR family of molecular pattern recognition receptors has been implicated in the induction of innate and adaptive immune responses. A role for TLR signaling in the maintenance and/or regulation of Treg function has been proposed, however its functional relevance remains unclear. Here we have shown that TLR9 is highly expressed by human(More)
The differentiation of naive CD4(+) T lymphocytes into Th1 and Th2 lineages generates either cellular or humoral immune responses. Th2 cells express the cytokines IL-4, -5, and -13, which are implicated in asthma and atopy. Much has been published about the regulation of murine Th2 cytokine expression, but studies in human primary T cells are less common.(More)
Glucocorticoids are the mainstay of asthma therapy and mediate the repression of a number of cytokine genes, such as Interleukin (IL)-4, -5, -13, and granulocyte macrophage colony-stimulating factor (GM-CSF), which are central to the pathogenesis of asthmatic airway inflammation. The glucocorticoid receptor (GR) mediates repression by a number of diverse(More)
Rhinoviruses (RVs), which are the most common cause of virally induced asthma exacerbations, account for much of the burden of asthma in terms of morbidity, mortality, and associated cost. Interleukin-25 (IL-25) activates type 2-driven inflammation and is therefore potentially important in virally induced asthma exacerbations. To investigate this, we(More)
Thymic stromal lymphopoietin (TSLP) is said to increase expression of chemokines attracting Th2 T cells. We hypothesized that asthma is characterized by elevated bronchial mucosal expression of TSLP and Th2-attracting, but not Th1-attracting, chemokines as compared with controls, with selective accumulation of cells bearing receptors for these chemokines.(More)
We have developed an in vitro differentiation assay in which human naive CD4(+) cells are driven toward either the Th1 or Th2 phenotype. We have examined the interrelationships among the expression of IL-2, IL-4, IL-5, IL-10, IL-13, GM-CSF, and IFN-gamma in individual cells using intracellular cytokine staining at various times during the differentiation(More)
BACKGROUND Increased proliferation of airway smooth muscle (ASM) cells leading to hyperplasia and increased ASM mass is one of the most characteristic features of airway remodelling in asthma. A bioactive lipid, sphingosine-1-phosphate (S1P), has been suggested to affect airway remodelling by stimulation of human ASM cell proliferation. OBJECTIVE To(More)
During the differentiation of naïve CD4+ precursors to T helper 1 (Th1) or Th2 effector cells, several epigenetic changes occur in a lineage-specific manner at the IFN-gamma or IL-4/IL-13 loci. These changes result in alterations in the chromatin structure of these loci and, hence, lineage-restricted expression of the corresponding cytokines. Intergenic(More)