Neuropilin-2 is a negative regulator of allergic airway inflammation

RATIONALE: Neuropilin-2 (NRP2) is an immunoregulatory protein that has both transmembrane and soluble forms. We have previously reported that inhaled endotoxin and house dust induce NRP2 expression in alveolar macrophages, suggesting that NRP2 may regulate inflammatory responses in the airways. Here, we have investigated the role of NRP2 in allergic airway inflammation.

METHODS: Using a house dust-mediated asthma model, we measured soluble NRP2 levels in bronchoalveolar lavage fluid (BALF) from wild type (WT) mice after allergen challenge. We compared allergic airway inflammation (airway eosinophilia, goblet cell metaplasia) in WT and NRP2-deficient (NRP2-KO) mice. Using semi-quantitative immunoblot analysis, we also measured soluble NRP2 levels in induced sputum from healthy volunteers (n = 8) and individuals with mild allergic asthma (n=8) under baseline conditions.

RESULTS: We found that BALF levels of soluble NRP2 were increased in a mouse model of house dust-mediated asthma. Genetic ablation of NRP2 led to enhanced allergic airway inflammation in mice. Compared to WT mice, NRP2-KO mice had increased numbers of total airway cells and eosinophils, and increased goblet cell metaplasia after allergen challenge. In human sputum samples, baseline median levels of soluble NRP2 were lower in allergic asthmatics (0.944 densitometry units) compared to healthy volunteers (2.409 densitometry units, P=0.0011).

CONCLUSIONS: NRP2 deficiency results in enhanced allergic airway inflammation in mice. Furthermore, decreased sputum levels of soluble NRP2 are associated with allergic asthma in humans. Collectively, these findings suggest that NRP2 is a negative regulator of allergic asthma.