Pathogenic helper T cells as the novel therapeutic targets for immune-mediated intractable diseases

• Published in: Pharmacology & therapeutics (Oxford) 2023-07, Vol.247, p.108445-108445, Article 108445
• Main Authors: Onodera, Atsushi, Kokubo, Kota, Okano, Mikiko, Onoue, Miki, Kiuchi, Masahiro, Iwamura, Chiaki, Iinuma, Tomohisa, Kimura, Motoko Y., Ebihara, Nobuyuki, Hanazawa, Toyoyuki, Nakayama, Toshinori, Hirahara, Kiyoshi
• Format: Article
• Language: English
• Subjects: Allergy; Biological agent; Cytokines; Dermatitis, Atopic; Humans; Hypersensitivity - drug therapy; Interleukin-5 - therapeutic use; JAK inhibitor; Pathogenic Th2 cell; Th2 cell; Th2 Cells
• ISSN: 0163-7258; 1879-016X
• DOI: 10.1016/j.pharmthera.2023.108445

Allergic diseases arise from a complex interplay between immune system and environmental factors. A link between the pathogenesis of allergic diseases and type 2 immune responses has become evident, with conventional and pathogenic type 2 helper T (Th2) cells involved in both. Recently, there has been a significant development in therapeutic agents for allergic diseases: IL-5 and IL-5 receptor antagonists, Janus kinase (JAK) inhibitors, and sublingual immunotherapy (SLIT). Mepolizumab, an IL-5, and Benralizumab, an IL-5 receptor antagonist, modulate eosinophilic inflammation mediated by IL-5-producing Th2 cells. Delgocitinib shows that JAK-associated signaling is essential for the inflammatory reaction in atopic dermatitis, one of the common allergic diseases. SLIT has a significant effect on allergic rhinitis by reducing pathogenic Th2 cell numbers. More recently, novel molecules that are involved in pathogenic Th2 cell-mediated allergic diseases have been identified. These include calcitonin gene-related peptide (CGRP), reactive oxygen species (ROS) scavenging machinery regulated by the Txnip-Nrf2-Blvrb axis, and myosin light chain 9 (Myl9), which interacts with CD69. This review provides an updated view of the recent research on treatment of allergic diseases and their cause: conventional and pathogenic Th2 cells.