Possible therapeutic use of L-type amino acid transporter 1 (LAT1)-specific inhibitor for intractable asthma treatment

Abstract

Bronchial asthma (asthma) is characterized by chronic airway inflammation, reversible obstruction, and hyperresponsive conditions. Although most asthma patients have been becoming controllable by virtue of inhaled corticosteroid (ICS), substantial number of patients still do not respond to the steroid-based therapy. Mast cells, eosinophils, and helper T (Th) 2 cells have been considered as key players in asthma pathogenesis. However, emerging studies have revealed that Th subsets other than Th2, as well as various other immune cells, significantly contribute to the development of steroid-resistant intractable asthma. T cells and other inflammatory cells require incorporating a large amount of nutrients such as amino acids and glucose to exhibit their full function following activation. Based on this remarkable character, it has recently been suggested that the pharmacological inhibition of amino acid transporters is promising for treating immunological and inflammatory disorders through the suppression of inflammatory cell activation. In this review, we explore the possible management of intractable asthma by developing a selective inhibitor for L-type amino acid transporter (LAT) 1.