Type 2 immunity in the skin and lungs

C A Akdis, Peter Arkwright, M C Bruggen, W Busse, M Gadina, E Guttman-Yassky, K Kabashima, Y Mitamura, L Vian, W Jianni, O Palomares

Research output: Contribution to journalArticlepeer-review

Abstract

There has been extensive progress in understanding the cellular and molecular
mechanisms of inflammation and immune regulation in allergic diseases of the skin and lungs during the last few years. Asthma and atopic dermatitis are typical diseases of type 2-immune responses. IL-25, IL-33 and TSLP are essential cytokines of epithelial cell that activation by allergens, pollutants, viruses, bacteria and toxins that derive type 2 responses. Th2 cells and innate lymphoid cells produce and secrete type 2 cytokines such as interleukin (IL)-4, IL-5, IL-9 and IL-13. IL-4 and IL-13 activate B cells to class switch to IgE and also play a role in T cell and eosinophil migration to allergic inflammatory tissues. IL-13 contributes to maturation, activation, nitric oxide production and differentiation of epithelia, production of mucus as well as smooth muscle contraction and extracellular matrix generation. IL-4 and IL-13 open tight junction barrier and cause barrier leakiness in the skin and lungs. IL-5 acts on activation, recruitment and survival of eosinophils. IL-9 contributes to general allergic phenotype by enhancing all of the aspects, such as IgE and eosinophilia. Type 2 innate lymphoid cells (ILC) contribute to inflammation in atopic dermatitis and asthma by enhancing the activity of Th2 cells, eosinophils and their cytokines. Currently five biologics are licensed to suppress type 2 inflammation via IgE, IL-5 and its receptor and IL-4 receptor alpha. Some patients with severe atopic disease have little evidence of type 2 hyperactivity and do not respond to biologics which target this pathway. Studies in responder and non-responder patients demonstrate the complexity of these diseases. In addition, primary immune deficiency diseases related to T cell maturation, regulatory T cell development, T cell signaling, such as Omenn syndrome, severe combined immune deficiencies, IPEX syndrome, DOCK8, STAT3 64 and CARD11 deficiencies help in our understanding of the importance and redundancy of various type 2 immune components. The present review aims to highlight recent advances in type 2 immunity and discuss the cellular sources, targets, and roles of type 2 mechanisms in asthma and atopic dermatitis.
Original languageEnglish
JournalAllergy
Publication statusAccepted/In press - 6 Apr 2020

Keywords

  • type 2 immunity
  • atopic dermatitis
  • asthma
  • biologics
  • ILC2

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