T-cell trafficking in asthma: lipid mediators grease the way

Abstract

Recruitment of T cells to the airways is crucial in the pathogenesis of asthma, and it is thought to be mediated mainly by peptide chemokines. By contrast, lipid mediators such as leukotrienes and prostaglandins have classically been thought to contribute to asthma pathogenesis by other mechanisms. However, as we discuss here, the recent molecular identification of leukotriene and prostaglandin receptors, as well as the generation of mice that are genetically deficient in them, has revealed that two of these lipids - leukotriene B(4) and prostaglandin D(2) - also direct T-cell migration and seem to cooperate with chemokines in a non-redundant, sequential manner to recruit T cells to the airways in asthma.

Control of T helper 2 cell function and allergic airway inflammation by PKCζ

“…These data validate PKC in asthma, because the mutant mice show a dramatically reduced response to OVAinduced airway inflammation. This response is the consequence of a complex set of cellular interactions involving the recruited Th2 lymphocytes and lung resident cells (1,11). Of note, adoptive transfer experiments reported in this study demonstrate that the loss of PKC in lung resident cells does not contribute significantly to the impairment of the inflammatory response in this system, whereas the loss of PKC in Th2 cells is of great importance.…”

The Type 1 Cysteinyl Leukotriene Receptor Triggers Calcium Influx and Chemotaxis in Mouse αβ- and γδ Effector T Cells

“…2, A and B). The mechanisms controlling the recruitment of T cells to inflamed lungs constitute an important focus of research on the pathogenesis of asthma (19). A model of Th2 cell trafficking in asthma has been proposed in which the lipid mediators LTB 4 and PGD 2 direct the earliest phases of T cell recruitment to the airways, whereas chemokines direct the subsequent phases of T cell recruitment that amplify and maintain airway inflammation (19 -23).…”

Loss of PKCλ/ι impairs Th2 establishment and allergic airway inflammation in vivo

“…Th2 cells produce a different set of cytokines, including IL-4, IL-5, IL-10, and IL-13, and are important in the control of humoral immunity and allergy (6). In this regard, the pathology of asthma, a chronic lung inflammatory disease with increased prevalence in developed countries (7), is associated with aberrant activation and/or differentiation of CD4 ϩ Th2 lymphocytes (8). The molecular mechanisms controlling Th2 differentiation and function have been the object of much research because of their relevance to inflammation disorders, such as asthma, for which better therapies are sorely needed, and because these mechanisms are a very interesting model system of crosstalk between different signaling cascades during a complex biological process.…”