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Type 2 inflammation

{{Short description|Pattern of immune response}}

{{distinguish|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.{{Cite journal|date=2014-08-01|title=Host protective roles of type 2 immunity: Parasite killing and tissue repair, flip sides of the same coin|journal=Seminars in Immunology|language=en|volume=26|issue=4|pages=329–340|doi=10.1016/j.smim.2014.06.003|issn=1044-5323|pmc=4179909|pmid=25028340|last1=Allen|first1=Judith E.|last2=Sutherland|first2=Tara E.}}{{Cite journal|last1=Gandhi|first1=Namita A.|last2=Bennett|first2=Brandy L.|last3=Graham|first3=Neil M. H.|last4=Pirozzi|first4=Gianluca|last5=Stahl|first5=Neil|last6=Yancopoulos|first6=George D.|date=2016-01-01|title=Targeting key proximal drivers of type 2 inflammation in disease|url=https://www.nature.com/articles/nrd4624|journal=Nature Reviews Drug Discovery|language=en|volume=15|issue=1|pages=35–50|doi=10.1038/nrd4624|pmid=26471366|s2cid=2421591|issn=1474-1784|url-access=subscription}}

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 (Th2 cells), type 2 innate lymphoid cells (ILC2 cells), and dendritic cells. Th2 cells and ILC2 cells secrete IL-4, IL-5 and IL-13.{{Cite journal|last1=Hong|first1=Haiyu|last2=Liao|first2=Shumin|last3=Chen|first3=Fenghong|last4=Yang|first4=Qintai|last5=Wang|first5=De-Yun|date=2020|title=Role of IL-25, IL-33, and TSLP in triggering united airway diseases toward type 2 inflammation|journal=Allergy|language=en|volume=75|issue=11|pages=2794–2804|doi=10.1111/all.14526|pmid=32737888|s2cid=220908481|issn=1398-9995|doi-access=free}}

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.

Dysregulation in human disease

Type 2 inflammation has been implicated in several chronic diseases:

  • Asthma{{Cite journal|last=Fahy|first=John V.|date=2015|title=Type 2 inflammation in asthma — present in most, absent in many|journal=Nature Reviews Immunology|language=en|volume=15|issue=1|pages=57–65|doi=10.1038/nri3786|issn=1474-1733|pmc=4390063|pmid=25534623}}{{Cite journal |last1=Akdis |first1=Cezmi A. |last2=Arkwright |first2=Peter D. |last3=Brüggen |first3=Marie-Charlotte |last4=Busse |first4=William |last5=Gadina |first5=Massimo |last6=Guttman-Yassky |first6=Emma |author-link6=Emma Guttman-Yassky |last7=Kabashima |first7=Kenji |last8=Mitamura |first8=Yasutaka |last9=Vian |first9=Laura |last10=Wu |first10=Jianni |last11=Palomares |first11=Oscar |date=2020 |title=Type 2 immunity in the skin and lungs |journal=Allergy |language=en |volume=75 |issue=7 |pages=1582–1605 |doi=10.1111/all.14318 |issn=1398-9995 |pmid=32319104 |s2cid=216075178 |doi-access=free}}
  • Atopic dermatitis
  • Chronic sinusitis with nasal polyps{{Cite journal|last1=Hulse|first1=K. E.|last2=Stevens|first2=W. W.|last3=Tan|first3=B. K.|last4=Schleimer|first4=R. P.|date=2015|title=Pathogenesis of nasal polyposis|journal=Clinical & Experimental Allergy|language=en|volume=45|issue=2|pages=328–346|doi=10.1111/cea.12472|pmc=4422388|pmid=25482020}}
  • Eosinophilic esophagitis{{Cite journal|last1=Hill|first1=David A.|last2=Spergel|first2=Jonathan M.|date=2016|title=The Immunologic Mechanisms of Eosinophilic Esophagitis|journal=Current Allergy and Asthma Reports|language=en|volume=16|issue=2|pages=9|doi=10.1007/s11882-015-0592-3|issn=1529-7322|pmc=4913464|pmid=26758862}}
  • Bullous pemphigoid{{Cite journal |last1=Werth |first1=Victoria P. |last2=Murrell |first2=Dédée F. |last3=Joly |first3=Pascal |last4=Heck |first4=Renata |last5=Orengo |first5=Jamie M. |last6=Ardeleanu |first6=Marius |last7=Hultsch |first7=Verena |date=2024-12-01 |title=Pathophysiology of Bullous Pemphigoid: Role of Type 2 Inflammation and Emerging Treatment Strategies (Narrative Review) |journal=Advances in Therapy |language=en |volume=41 |issue=12 |pages=4418–4432 |doi=10.1007/s12325-024-02992-w |issn=1865-8652 |pmc=11550233 |pmid=39425892}}

Persons with one type 2 inflammatory disease are more likely to have other type 2 inflammatory diseases.{{Cite journal|last1=Khan|first1=Asif|last2=Gouia|first2=Imène|last3=Kamat|first3=Siddhesh|last4=Ortiz|first4=Benjamin|last5=Johnson|first5=Robert|last6=Siddall|first6=James|last7=Small|first7=Mark|date=2020-09-07|title=Type 2 inflammation-related comorbidities among patients with asthma, chronic rhinosinusitis with nasal polyps, and atopic dermatitis|url=https://erj.ersjournals.com/content/56/suppl_64/232|journal=European Respiratory Journal|language=en|volume=56|issue=suppl 64|page=232|doi=10.1183/13993003.congress-2020.232|s2cid=229017279 |issn=0903-1936|url-access=subscription}}

Pharmacological targets

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

References

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Category:Immunology

Category:Asthma

Category:Atopic dermatitis