Comparative analysis of the role of mast cells in murine asthma models using Kit-sufficient mast cell-deficient animals.

Background: Asthma is a frequent chronic disease that can potentially severely affect the respiratory capacity and well-being of patients. Mast cells (MCs) are regarded as major players in human asthma due to their capacity to release crucial inflammatory mediators following allergen exposure. However, unambiguous characterization of their role in animal models has long been hindered by the unavailability of specific MC-deficient models lacking confounding MC-unrelated effects.

IL-21 promotes allergic airway inflammation by driving apoptosis of FoxP3 regulatory T cells.

Background: IL-21 is a key player of adaptive immunity, with well-established roles in B-cell and cytotoxic T-cell responses. IL-21 has been implicated in promotion of effector CD4 T cells and inhibition of forkhead box P3-positive regulatory T (Treg) cells, but the mechanism and functional relevance of these findings remain controversial.

Objective: We sought to understand the mechanisms by which IL-21 controls effector CD4 cell responses and Treg cell homeostasis.

Clara epithelial cell depletion in the lung.

The bronchial epithelium has been increasingly recognized as an important immunomodulatory compartment in asthma and other lung diseases. Clara cells, which comprise the nonciliated secretory epithelial cells, are an important epithelial cell type with functions in the regulation of lung homeostasis and inflammation. Using naphthalene, Clara cells can be depleted within 24 h and regenerate by 1 month, hence, providing an easy method to study the impact of Clara cells on lung inflammation.

Linking surfactant protein SP-D and IL-13: implications in asthma and allergy.

Surfactant protein D (SP-D) is an innate immune molecule that plays a protective role against lung infection, allergy, asthma and inflammation. In vivo experiments with murine models have shown that SP-D can protect against allergic challenge via a range of mechanisms including inhibition of allergen-IgE interaction, histamine release by sensitised mast cells, downregulation of specific IgE production, suppression of pulmonary and peripheral eosinophilia, inhibition of mechanisms that cause airway remodelling, and induction of apoptosis in sensitised eosinophils. SP-D can also shift helper T cell polarisation following in vivo allergenic challenge, from pathogenic Th2 to a protective Th1 cytokine response.

Nerve growth factor induces type III collagen production in chronic allergic airway inflammation.

Background: Excessive extracellular matrix deposition occurs as a result of repetitive injury-repair cycles and plays a central role in the pathogenesis of chronic inflammatory diseases, such as allergic asthma. The molecular mechanism leading to aberrant collagen deposition is not fully understood.

Objective: We sought to test the hypothesis that increased nerve growth factor (NGF) production contributes to collagen deposition in the airways during chronic allergic airway inflammation.

Antagonism of TIM-1 blocks the development of disease in a humanized mouse model of allergic asthma.

Studies in mice and humans have revealed that the T cell, immunoglobulin, mucin (TIM) genes are associated with several atopic diseases. TIM-1 is a type I membrane protein that is expressed on T cells upon stimulation and has been shown to modulate their activation. In addition to a recently described interaction with dendritic cells, TIM-1 has also been identified as a phosphatidylserine recognition molecule, and several protein ligands have been proposed.

Therapeutic effects of recombinant forms of full-length and truncated human surfactant protein D in a murine model of invasive pulmonary aspergillosis.

Aspergillus fumigatus (Afu) is an opportunistic fungal pathogen that can cause fatal invasive pulmonary aspergillosis (IPA) in immunocompromised individuals. Previously, surfactant protein D (SP-D), a surfactant-associated innate immune molecule, has been shown to enhance phagocytosis and killing of Afu conidia by phagocytic cells in vitro. An intranasal treatment of SP-D significantly increased survival in a murine model of IPA.

Nerve growth factor and neurotrophin-3 mediate survival of pulmonary plasma cells during the allergic airway inflammation.

Allergen-specific Abs play a pivotal role in the induction and maintenance of allergic airway inflammation. During secondary immune responses, plasma cell survival and Ab production is mediated by extrinsic factors provided by the local environment (survival niches). It is unknown whether neurotrophins, a characteristic marker of allergic airway inflammation, influence plasma cell survival in the lung.