Predominance of Th2 Cytokines in AD

Th2 cytokines—including IL-13— play a key role in driving the amplification of the inflammatory response associated with AD.1

Non-lesional Skin

  • Due to immune dysregulation, non-lesional AD skin is characterized by subclinical inflammation as well as skin-barrier dysfunction1
  • Dendritic cells take up antigens and amplify type 2 immunity cytokines1
  • Worsened skin-barrier dysfunction can stimulate keratinocytes to further promote type 2 inflammation through the release of skin alarmins, such as IL-25, IL-33, and TSLP, which stimulate ILC2s to release more type 2 cytokines such as IL-13 and IL-51

Acute Lesional Skin

  • Acute lesional skin is characterized by a reduced expression of important skin-barrier proteins and lipids involved in maintaining skin-barrier integrity1
  • The damage caused to the skin barrier triggers the release of further skin alarmins, expanding and activating skin-resident ILC2 cells to produce more cytokines, attracting more immune cells, and amplifying the inflammatory response, including the recruitment of more eosinophils, Th2 cells, and Th22 cells—producing more cytokines1
  • Both IL-33 and TSLP, as well as the downstream Th2 cytokines (IL-4, IL-13, and IL-31), act directly on cutaneous sensory neurons, activating itch signaling and leading to scratching1
  • During an AD flare there is a decreased microbial diversity, with increased presence of Staphylococcus aureus1

Chronic Lesional Skin

  • In the chronic stage, a mixed T-cell infiltrate, including Th1 and Th17 cells, perpetuates skin inflammation and promotes skin remodeling and fibrosis1
  • Repetitive scratching leads to lichenified (thickened) skin1

ILC, innate lymphoid cell; TSLP, thymic stromal lymphopoietin.

Th2 cytokines, such as IL-13, play a key role in AD signs and symptoms, including skin barrier defects and infections, inflammation, skin thickening, and promoting the itch-scratch cycle.1-9

Discover the role of IL-13

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    J Invest Dermatol. 2011;131(3):655-661.
  9. Mack MR, Kim BS. The itch-scratch cycle: a neuroimmune perspective. Trends Immunol. 2018;39(12):980-991.