Pattern of immune response
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 (Th 2 cells), type 2 innate lymphoid cells (ILC2 cells), and dendritic cells . Th 2 cells and ILC2 cells secrete IL-4 , IL-5 and IL-13 .[ 1] [ 3]
IL-4 further drives CD4+ T cell differentiation towards the Th 2 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.[ 9]
Pharmacological targets
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
^ 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 . ^ 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 .
