Biological Sex\nIs an Effect Modifier of Allergen-Mediated\nAlteration of the Lung Proteome

Asthma exhibits a distinct sex bias\nin the disease prevalence,\nseverity, and response to therapy. However, sex-related differences\nin alterations of the lung proteome mediated by aeroallergens critical\nin asthma, such as house dust mites (HDM), remain unknown. In this\nstudy, we define sex-related differences in the lung proteome using\nan HDM-challenged mouse model by 1D LC–MS/MS. Sex-disaggregated\ndata analysis showed that 406 proteins were uniquely altered in females,\n273 proteins were uniquely altered in males, and 414 proteins were\naltered in both females and males in response to HDM. In a linear\nmixed model analysis, sex modified the HDM exposure effect for 163\nproteins, i.e., a significant sex:exposure interaction was identified\nin 84 proteins in females and 35 proteins in males. Of these, 12 proteins\nshowed a significant sex effect in both female and male lungs. We\nfurther selected 3 proteins Tjp1, Lamtor1, and G3BP2 for independent\nconfirmation studies. Our findings detail the sex-specific lung proteome\nin response to an aeroallergen critical in asthma and demonstrate\nthat sex is a significant effect modifier of HDM response. These results\nwill serve as a valuable resource for delineating sex-specific mechanisms\nin aeroallergen-driven responses in asthma research.