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. Interestingly,
SP-D gene deficient (-/-) mice show an
IL-13 over-expressing phenotype.
IL-13 has been shown to be involved in the development of
asthma. Transgenic mice over-expressing
IL-13 in the lung develop several characteristics of
asthma such as
pulmonary eosinophilia, airway epithelial
hyperplasia, mucus cell
metaplasia, sub-epithelial
fibrosis, charcot-Leyden-Like crystals, airways obstruction, and non-specific airways hyper-responsiveness to
cholinergic stimulation. Although both
IL-4 and
IL-13 are capable of inducing
asthma like phenotype, the effector activity of
IL-13 appears to be greater than that of
IL-4.
SP-D -/- mice seem to express considerably higher levels of
IL-13, which is consistent with increased sensitivity and exaggerated immune response of the mice to allergenic challenge. Allergenic exposure also induces elevation in
SP-D protein levels in an IL-4/
IL-13-dependent manner, which prevents further activation of sensitised T cells. This negative feedback loop seems essential in protecting the airways from inflammatory damage after
allergen inhalation. Here, we examine this link between
IL-13 and
SP-D, and its implications in the progression/regulation of
asthma and
allergy.