Mouse eosinophil‐associated ribonuclease‐2 exacerbates the allergic response
La mERA2 des éosinophiles murins aggrave la réponse allergique
Résumé
Background: Eosinophil’s granule cytotoxic proteins, including eosinophil-derived neurotoxin (EDN), have an important role in the pathogenesis of eosinophilic inflammation such as allergic asthma. In the murine, mouse eosinophil-associated ribonuclease-2 (mEAR2) was considered as the murine orthologue of human EDN. However, underlying mechanisms of mEAR2 and EDN action in pathological of allergic asthma remains poorly understood.
Methods: To investigate the role of mEAR2, Airway Allergic Inflammation (AAI) was induced by house dust mite (HDM) in genetically modified mice in which exon 2 in the mEAR2 was deleted (mEAR2-/-). Airway hyperresponsiveness (AHR), lung histopathological, bronchoalveolar lavage fluid (BALF) analysis, mEAR2 level analysis, total Immunoglobulin E (IgE) levels and cytokines profiling were performed. Sensitized splenocytes and bone marrow derived eosinophils (bmEOS) were co-cultured with or without HDM and TLR2 antibody to investigate IL-4, -5, and -13 level in the supernatant.
Results: We found that mEAR2 concentration was significantly increased in the lung tissue from mEAR2+/+ but not mEAR2-/- mice in AAI. In sensitized and challenged mEAR2-/- mice type 2 cytokines and IgE concentrations were significantly decreased. HDM-sensitized bmEOS from mEAR2+/+ but not from mEAR2-/- mice increased type 2 cytokine production by cocultured splenocytes 4and this increase was completely inhibited in the presence of TLR2 antibody.
Conclusion: These data suggest that mEAR2 exacerbates pathogenesis of AAI in a TLR2-dependent manner.