Type 2 inflammation

Not to be confused with type II hypersensitivity.

Type 2 inflammation is a pattern of immune response. Its physiological function is to defend the body against helminths, but a dysregulation of the type 2 inflammatory response has been implicated in the pathophysiology of several diseases.^[1][2]

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 (T_h2 cells), type 2 innate lymphoid cells (ILC2 cells), and dendritic cells. T_h2 cells and ILC2 cells secrete IL-4, IL-5 and IL-13.^[1][3]

IL-4 further drives CD4+ T cell differentiation towards the T_h2 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.^[2]

Dysregulation in human disease

Type 2 inflammation has been implicated in several chronic diseases:

• Asthma^[4][5]
• Atopic dermatitis^[5]
• Chronic sinusitis with nasal polyps^[6]
• Eosinophilic esophagitis^[7]
• Bullous pemphigoid^[8]

Persons with one type 2 inflammatory disease are more likely to have other type 2 inflammatory diseases.^[9]

Pharmacological targets

Several medicines have been developed that target mediators of type 2 inflammation:^[2]

• 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