Type 2 inflammation

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:

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:^[2]

IL-4-specific blockers:
- Altrakincept
- Pascolizumab
IL-5-specific blockers:
IL-13-specific blockers:
- Lebrikizumab
- Tralokinumab
Dual IL-4 and IL-13 blockers:
- Dupilumab
IgE-blockers:
- Ligelizumab
- Omalizumab

References

^ ^a ^b 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.
^ ^a ^b ^c 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.
^ 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.
^ ^a ^b 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.
^ 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.

[:0-1] 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] 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.

[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. 75 (11): 2794–2804. doi:10.1111/all.14526. ISSN 1398-9995. PMID 32737888. S2CID 220908481.

[4] 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.

[:2-5] 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.

[6] 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.

[7] 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.

[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. 56 (suppl 64): 232. doi:10.1183/13993003.congress-2020.232. ISSN 0903-1936. S2CID 229017279.

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