%0 Journal Article %A George Scott %A Jeanne Allinne %A Seblewongel Asrat %A Weikeat Lim %A Kirsten Nagashima %A Dylan Birchard %A Subhashini Srivatsan %A Dharani Ajithdoss %A Adelekan Oyejide %A Li-Hong Ben %A Johnathon Walls %A Audrey Le Floc'H %A George Yancopoulos %A Andrew Murphy %A Matthew Sleeman %A Jamie Orengo %T Comparison of transcriptional differences between IL-4Ra and IL-5 blockade in a mouse model of asthma %D 2021 %R 10.1183/13993003.congress-2021.PA674 %J European Respiratory Journal %P PA674 %V 58 %N suppl 65 %X Rationale:  Biologics directed against effectors of type 2 inflammation improve signs and symptoms of asthma by different  mechanisms  that have not been fully elucidated.  Aim:  Determine the complete extent of transcription differences and similarities downstream of IL-4Rα and IL-5 blockade in a disease relevant model of asthma.Methods: Mice  were exposed to house dust mite  for 4 weeks  and  received twice‐weekly subcutaneous  injections of  anti-IL-4Rα  (dupilumab)  or  anti‐IL‐5.  Gene expression changes in the lung were analyzed by bulk RNA-sequencing.   Results: HDM alone significantly perturbed over 700 genes, 208 of which were affected by anti-IL-4Rα  (inversely perturbed). There were 8 HDM responsive genes in common between the two antibody treatments. Interestingly, these genes were related to eosinophilia.  Lastly, this study only found 1 HDM responsive gene  that  overlapped with  anti-IL-5 treatment.Conclusion: The results show that IL-5 blockade has highly specific effects on eosinophil function, whereas IL-4Rα blockade impacts genes associated with eosinophils, but also has a much broader effect, impacting genes involved in mucus production and secretion, airway remodeling, bronchoconstriction and hyperresponsiveness.FootnotesCite this article as: European Respiratory Journal 2021; 58: Suppl. 65, PA674.This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). %U