Type 2 inflammation (or type 2 immunity) is a pattern of immune response. Its physiological function is to defend the body against helminths, but a dysregulation of the type 2 immune response has been implicated in the pathophysiology of several diseases. Although it has traditionally been associated with tumor promotion, emerging evidence indicates a tumor-suppressive potential.
Molecular biology IL-25, IL-33, and TSLP are alarmins released from damaged epithelial cells. These cytokines mediate the activation of type 2 T helper cells (Th2 cells), group 2 innate lymphoid cells (ILC2 cells), and dendritic cells. Th2 cells and ILC2 cells secrete IL-4, IL-5 and IL-13. IL-4 further drives CD4+ T cell differentiation towards the Th2 subtype and induces isotype switching to IgE in B cells. IL-4 and IL-13 stimulate trafficking of eosinophils to the site of inflammation, while IL-5 promotes both eosinophil trafficking and production.
Dysregulation in human disease Type 2 inflammation has been implicated in several chronic diseases:
Asthma Atopic dermatitis Chronic sinusitis with nasal polyps Eosinophilic esophagitis Bullous pemphigoid Persons with one type 2 inflammatory disease are more likely to have other diseases.
Pharmacological targets Several medicines have been developed that target mediators of type 2 inflammation:
IL-4-specific blockers: Altrakincept Pascolizumab IL-5-specific blockers: Benralizumab Mepolizumab Reslizumab IL-13-specific blockers: Lebrikizumab Tralokinumab Dual IL-4 and IL-13 blockers: Dupilumab IgE-blockers: Ligelizumab Omalizumab
References