Type 2 inflammation
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.[1][2] Although it has traditionally been associated with tumor promotion, emerging evidence indicates a tumor-suppressive potential.[3]
Molecular biology
[edit]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.[1][4]
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.[2]
Dysregulation in human disease
[edit]Type 2 inflammation has been implicated in several chronic diseases:
- Asthma[5][6]
- Atopic dermatitis[6]
- Chronic sinusitis with nasal polyps[7]
- Eosinophilic esophagitis[8]
- Bullous pemphigoid[9]
Persons with one type 2 inflammatory disease are more likely to have other diseases.[10]
Pharmacological targets
[edit]Several medicines have been developed that target mediators of type 2 inflammation:[2]
- IL-4-specific blockers:
- IL-5-specific blockers:
- IL-13-specific blockers:
- Dual IL-4 and IL-13 blockers:
- IgE-blockers:
References
[edit]- 1 2 Allen, Judith E.; Sutherland, Tara E. (2014-08-01). "Host protective roles of type 2 immunity: Parasite killing and tissue repair, flip sides of the same coin". Seminars in Immunology. 26 (4): 329–340. doi:10.1016/j.smim.2014.06.003. ISSN 1044-5323. PMC 4179909. PMID 25028340.
- 1 2 3 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. 15 (1): 35–50. doi:10.1038/nrd4624. ISSN 1474-1784. PMID 26471366. S2CID 2421591.
- ↑ Wagner, Marek; Nishikawa, Hiroyoshi; Koyasu, Shigeo (January 2025). "Reinventing type 2 immunity in cancer". Nature. 637 (8045): 296–303. Bibcode:2025Natur.637..296W. doi:10.1038/s41586-024-08194-2. ISSN 1476-4687. PMID 39780006.
- ↑ 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. 75 (11): 2794–2804. doi:10.1111/all.14526. ISSN 1398-9995. PMID 32737888. S2CID 220908481.
- ↑ Fahy, John V. (2015). "Type 2 inflammation in asthma — present in most, absent in many". Nature Reviews Immunology. 15 (1): 57–65. doi:10.1038/nri3786. ISSN 1474-1733. PMC 4390063. PMID 25534623.
- 1 2 Akdis, Cezmi A.; Arkwright, Peter D.; Brüggen, Marie-Charlotte; Busse, William; Gadina, Massimo; Guttman-Yassky, Emma; Kabashima, Kenji; Mitamura, Yasutaka; Vian, Laura; Wu, Jianni; Palomares, Oscar (2020). "Type 2 immunity in the skin and lungs". Allergy. 75 (7): 1582–1605. doi:10.1111/all.14318. ISSN 1398-9995. PMID 32319104. S2CID 216075178.
- ↑ Hulse, K. E.; Stevens, W. W.; Tan, B. K.; Schleimer, R. P. (2015). "Pathogenesis of nasal polyposis". Clinical & Experimental Allergy. 45 (2): 328–346. doi:10.1111/cea.12472. PMC 4422388. PMID 25482020.
- ↑ Hill, David A.; Spergel, Jonathan M. (2016). "The Immunologic Mechanisms of Eosinophilic Esophagitis". Current Allergy and Asthma Reports. 16 (2): 9. doi:10.1007/s11882-015-0592-3. ISSN 1529-7322. PMC 4913464. PMID 26758862.
- ↑ Werth, Victoria P.; Murrell, Dédée F.; Joly, Pascal; Heck, Renata; Orengo, Jamie M.; Ardeleanu, Marius; Hultsch, Verena (2024-12-01). "Pathophysiology of Bullous Pemphigoid: Role of Type 2 Inflammation and Emerging Treatment Strategies (Narrative Review)". Advances in Therapy. 41 (12): 4418–4432. doi:10.1007/s12325-024-02992-w. ISSN 1865-8652. PMC 11550233. PMID 39425892.
- ↑ 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. 56 (suppl 64): 232. doi:10.1183/13993003.congress-2020.232. ISSN 0903-1936. S2CID 229017279.