Journal
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Volume 145, Issue 6, Pages 1485-1497Publisher
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2020.02.021
Keywords
Atopic dermatitis; food allergy; skin barrier; peanut allergy; epithelial barrier
Categories
Funding
- National Institutes of Health (NIH)/National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01 AR41256]
- NIH/National Institute of Allergy and Infectious Diseases [U19 AI117673]
- NIH/National Center for Research Resources [UL1 RR025780]
- Edelstein Family Chair of Pediatric Allergy-Immunology at National Jewish Health
Ask authors/readers for more resources
The fundamental defect(s) that drives atopic dermatitis (AD) remains controversial. Outside in proponents point to the important association of filaggrin gene mutations and other skin barrier defects with AD. The inside out proponents derive support from evidence that AD occurs in genetic animal models with overexpression of type 2 immune pathways in their skin, and humans with gain-of-function mutations in their type 2 response develop severe AD. The observation that therapeutic biologics, targeting type 2 immune responses, can reverse AD provides compelling support for the importance of inside out mechanisms of AD. In this review, we propose a central role for epithelial cell dysfunction that accounts for the dual role of skin barrier defects and immune pathway activation in AD. The complexity of AD has its roots in the dysfunction of the epithelial barrier that allows the penetration of allergens, irritants, and microbes into a cutaneous milieu that facilitates the induction of type 2 immune responses. The AD phenotypes and endotypes that result in chronic skin inflammation and barrier dysfunction are modified by genes, innate/adaptive immune responses, and different environmental factors that cause skin barrier dysfunction. There is also compelling evidence that skin barrier dysfunction can alter the course of childhood asthma, food allergy, and allergic rhinosinusitis. Effective management of AD requires a multipronged approach, not only restoring cutaneous barrier function, microbial flora, and immune homeostasis but also enhancing skin epithelial differentiation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available