Th2-Cell-Mediated Chemokine Synthesis Is Involved in Allergic Airway Inflammation in Mice

Abstract

Eosinophilic inflammation in the bronchial mucosa has been recognized as a prominent pathological feature of bronchial asthma. Th2 cells have been implicated in the local infiltration and activation of eosinophils. The migration of eosinophils as well as Th2 cells is controlled by chemokines, suggesting a crucial role of chemokines in the pathogenesis of bronchial asthma. To elucidate the mechanism by which Th2 cells induce eosinophilic inflammation, a Th2-cell-dependent murine model of asthma was employed in this study. Along with the infiltration of eosinophils and antigen-specific Th2 cells, CC chemokine receptor-3-active eotaxin, monocyte chemoattractant protein (MCP)-3 and RANTES, as well as CC chemokine receptor-3-inactive MCP-1 were produced in the lungs of Th2-cell-transferred mice after antigen provocation in vivo. On the other hand, differentiated antigen-specific Th2 cells produced MCP-3 and RANTES but not eotaxin or MCP-1 upon stimulation in vitro. Chemokines synthesized by Th2 cells and other cell types are involved in the development of eosinophilic inflammation in bronchial asthma.

Selective down‐regulation of Th2 cell‐mediated airway inflammation in mice by pharmacological intervention of CCR4

“…However, the results are still controversial and the potential efficacy of CCR4 blockers in allergic disorders associated with eosinophilic inflammation remains unclear. We have generated an allergic airway inflammation model in which mice are transferred with in vitro-polarized OVA-specific Th1, Th2, or Th17 cells and challenged with OVA [26][27][28]. We have generated an allergic airway inflammation model in which mice are transferred with in vitro-polarized OVA-specific Th1, Th2, or Th17 cells and challenged with OVA [26][27][28].…”

“…The model has provided relatively consistent and reproducible results and thereby enables us to easily evaluate the efficacy of antibodies and chemical compounds [26][27][28]. The model has provided relatively consistent and reproducible results and thereby enables us to easily evaluate the efficacy of antibodies and chemical compounds [26][27][28].…”

“…We have developed a mouse model of airway inflammation in which mice are transferred with in vitro-differentiated T cells and challenged with the corresponding antigen. The model has provided relatively consistent and reproducible results and thereby enables us to easily evaluate the efficacy of antibodies and chemical compounds [26][27][28]. Herein, we employed this model to evaluate the role of CCR4 in the development of allergic inflammation by using Compound 22.…”

Allergen-Induced Airway Remodeling Is Impaired in Galectin-3–Deficient Mice

“…Reduced eotaxin-1 levels in the lungs of allergen-challenged Gal-3 KO mice may be due to reduced infiltration of the airways by inflammatory cells that release eotaxin-1 such as Th2 cells, alveolar macrophages and/or eosinophils themselves, or due to decreased IL-13-induced production of this chemokine by lung cells. Chemokines synthesized by Th2 cells and other cell types are involved in the development of eosinophilic inflammation in bronchial asthma and studies using a Th2-cell-dependent murine model of asthma have shown that infiltration of eosinophils and antigen-specific Th2 cells is associated with eotaxin, MCP-3, RANTES and MCP-1 in the lungs of Th2-cell-transferred mice after antigen provocation (49). In the present study, in addition to eotaxin-1, expression of MCP-1 in the lung tissue of chronic allergen-challenged Gal-3 KO mice was also inhibited (data not shown).…”

Allergic airway inflammation and susceptibility to pneumococcal pneumonia in a murine model with real-timein vivoevaluation

“…Non-sensitized mice, despite the strong Th1 response elicited by exposure to S. pneumoniae, had comparable (IL-4 and IL-5) or higher levels (IL-10 and IL-13) of Th2 cytokines and chemokines associated with airway inflammation (e.g. RANTES and eotaxin) [42,43] compared with sensitized mice. These data suggest that mice sensitized with OVA might not have the expected classic Th2 immune responses and non-sensitized mice might have undiminished Th2 responses for unknown reasons.…”