Type 2 inflammation explained

Type 2 inflammation should not 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.^[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.

Dysregulation in human disease

Type 2 inflammation has been implicated in several chronic diseases:

• Asthma^{[4] [5]}
• Atopic dermatitis
• Chronic sinusitis with nasal polyps^[6]
• Eosinophilic esophagitis^[7]

Persons with one type 2 inflammatory disease are more likely to have other type 2 inflammatory diseases.^[8]

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

Notes and References

1. 2014-08-01. Host protective roles of type 2 immunity: Parasite killing and tissue repair, flip sides of the same coin. Seminars in Immunology. en. 26. 4. 329–340. 10.1016/j.smim.2014.06.003. 1044-5323. 4179909. 25028340. Allen. Judith E.. Sutherland. Tara E..
2. Gandhi. Namita A.. Bennett. Brandy L.. Graham. Neil M. H.. Pirozzi. Gianluca. Stahl. Neil. Yancopoulos. George D.. 2016-01-01. Targeting key proximal drivers of type 2 inflammation in disease. Nature Reviews Drug Discovery. en. 15. 1. 35–50. 10.1038/nrd4624. 26471366. 2421591. 1474-1784.
3. Hong. Haiyu. Liao. Shumin. Chen. Fenghong. Yang. Qintai. Wang. De-Yun. 2020. Role of IL-25, IL-33, and TSLP in triggering united airway diseases toward type 2 inflammation. Allergy. en. 75. 11. 2794–2804. 10.1111/all.14526. 32737888. 220908481. 1398-9995. free.
4. Fahy. John V.. 2015. Type 2 inflammation in asthma — present in most, absent in many. Nature Reviews Immunology. en. 15. 1. 57–65. 10.1038/nri3786. 1474-1733. 4390063. 25534623.
5. Akdis . Cezmi A. . Arkwright . Peter D. . Brüggen . Marie-Charlotte . Busse . William . Gadina . Massimo . Guttman-Yassky . Emma . Emma Guttman-Yassky . Kabashima . Kenji . Mitamura . Yasutaka . Vian . Laura . Wu . Jianni . Palomares . Oscar . 2020 . Type 2 immunity in the skin and lungs . Allergy . en . 75 . 7 . 1582–1605 . 10.1111/all.14318 . 1398-9995 . 32319104 . 216075178 . free.
6. Hulse. K. E.. Stevens. W. W.. Tan. B. K.. Schleimer. R. P.. 2015. Pathogenesis of nasal polyposis. Clinical & Experimental Allergy. en. 45. 2. 328–346. 10.1111/cea.12472. 4422388. 25482020.
7. Hill. David A.. Spergel. Jonathan M.. 2016. The Immunologic Mechanisms of Eosinophilic Esophagitis. Current Allergy and Asthma Reports. en. 16. 2. 9. 10.1007/s11882-015-0592-3. 1529-7322. 4913464. 26758862.
8. Khan. Asif. Gouia. Imène. Kamat. Siddhesh. Ortiz. Benjamin. Johnson. Robert. Siddall. James. Small. Mark. 2020-09-07. Type 2 inflammation-related comorbidities among patients with asthma, chronic rhinosinusitis with nasal polyps, and atopic dermatitis. European Respiratory Journal. en. 56. suppl 64. 232. 10.1183/13993003.congress-2020.232. 229017279 . 0903-1936.