IL-5 Receptor Alpha Positive Lungs Cells Protect Against Acute Lung Injury 2257777

Abstract Introduction Acute Lung Injury (ALI) has a variety of etiologies that ultimately result in barrier dysfunction, which can lead to edema and hypoxemic respiratory failure. Previously, we demonstrated that IL-5 signaling has a protective effect on mice in the bleomycin mouse model of ALI. Mice lacking IL- 5Rα succumb to ALI and have more edema in the lung while treatment with IL-5 protects mice. Interestingly, these effects where independent of eosinophils suggesting a role for other IL-5 responding cells. We discovered that epithelial cells increased their expression of IL-5Rα seven days post bleomycin and that these IL-5Rα+ epithelial cells were highly proliferative. Additionally, IL-5Rα-positive B cells were increased in the lung tissue seven days post bleomycin administration, whereas eosinophil levels were comparable to uninjured mice. Methods To investigate the requirement of IL-5Rα in epithelial and B cells during bleomycin, a Cre-lox mouse model was utilized to specifically of delete IL-5Rα in these populations. These conditional knockouts were then subjected to bleomycin-induced ALI. Results While IL-5Rα+ epithelial cells are more proliferative, conditional depletion of IL-5Rα in lung epithelium did not impact survival during ALI. Depletion of IL-5Rα in B cells also did not have a difference in survival compared to controls however, B cell subsets were skewed towards B-2 cells. This suggests that multiple cell types are responding to IL-5 and their effect alone may not affect protection during bleomycin induced acute lung injury. Conclusion During bleomycin-induced ALI, exogenous IL-5 is protective, and we demonstrate that both lung epithelial cells and B cells respond to IL-5 through proliferation and subset differentiation, respectively. It is possible multiple IL-5 responding cells are together involved in protective mechanisms during ALI. As IL-5 signaling is a target in the clinic for reducing eosinophils, this novel IL-5 protective pathway during ALI should be considered in these patients. Funding Source T32 AI007046 Topic Categories Mucosal and Regional Immunology (MUC)