The mold allergen Alt a 1 is related to asthma vía its interaction with the lung receptor SLC22A17

Alternaria alternata is the most important mold allergen related to respiratory allergies and severe asthma, especially in children. Only in South Europe, over 20% of the patients with respiratory allergy showed sensitization to Alternaria, being Alt a 1 the most prevalent allergen. Alt a 1 can assemble as a tetramer, only in the presence of its ligand, similar to quercetin, recently identified in our group. Focusing on the interaction of Alt a 1 and the human airway epithelium, our study has demonstrated that the ligand of Alt a 1 is responsible for immunological activation. Using in-vitro and in-vivo assays, we have found that Alt a 1 can be recognized by the epithelium, inducing a pro-inflammatory response. This interaction is mediated by an immunological receptor (SLC22A17), that also can recognize the human siderocalin. Our results revealed that only with the ligand, the holo-form, can bind to the receptor. This finding was complemented with in silico studies showing that Alt a 1 bears structural resemblance with siderocalin. Therefore, our work could provide essential clues to unveil the entry route of this fungal allergen in the epithelium, ultimately leading to asthma.