Abstract
Sex differences in the incidence and severity of pulmonary inflammatory diseases such as asthma in favor of women have been reported. Studies shows that estrogen signalling is not limited to genomic mechanism, but it can interact with multiple cytoplasmatic signalling networks, including sphingosine-1-phosphate (S1P). S1P mediates lymphocyte trafficking in immunity and allergy but also shows an intrinsic function in both innate and adaptive immune system. Here we have defined a sex bias in S1P pulmonary effects. Systemic administration of S1P, without adjuvant factors, promoted in the mouse a disease closely mimicking the cardinal features of severe asthma such as airway hyperreactivity (AHR), lung eosinophils inflammation, high circulating levels of IgE, and predominace of CD4+ T cell-derived IL-4. This asthma like phenotype developed only in females. On the other hand, treatment of allergen sensitization male and female mice with L-cycloserine, an inhibitor of S1P synthesis, prevented asthma features only in females. Furthermore, functional study conducted on bronchial tissues harvested from atopic mice proved a sex bias in the regulation of basal bronchial tone driven by S1P. Bronchi harvested from female mice showed an increased reactivity compared to males. Inhibition of S1P signalling abrogated sex bias in bronchial reactivity. This result was confirmed by real-time PCR analysis showing an increased expression of S1P kinases and receptors in bronchi harvested from females compared to males. In conclusion, these data proved that S1P pathway is involved in sex bias in the lung. This sex difference of S1P signalling in asthma like-features should be considered for a sex-tailored therapy in allergic disorders.
Footnotes
Cite this article as ERJ Open Research 2022; 8: Suppl. 8, 207.
This article was presented at the 2022 ERS Lung Science Conference, in session “Poster Session 2”.
This is an ERS Lung Science Conference 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).
- Copyright ©the authors 2022