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Spotlight on AD—the role key cytokines play and a look at the factors that contribute to this condition

Author : Sanofi
Editorial Team

Beneath the skin of patients with AD—type 2 inflammation and the cytokines involved.

Contributing factors in atopic dermatitis (AD)

AD has a complex, multifactorial pathophysiology, driven by an interplay between1-3:

UnderlyingIcon

underlying chronic type 2 immune dysregulation2,3

EpidermalIcon

epidermal barrier dysfunction1

GeneticIcon

genetic factors2,3

EnviromentalIcon

environmental factors2,3

Several immune cells are involved in type 2 inflammation, including ILC2 cells, Th2 cells, mast cells, and eosinophils, and they produce type 2 cytokines such as IL-4, IL-13, and IL-31.4

Activation of type 2 inflammatory pathways results in the release of type 2 inflammatory cytokines. These cytokines include IL-4, IL-13, and IL-31.3,5

IL-4 is required for the differentiation of T cells from naive T helper 0 (Th0) to T helper 2 (Th2) that drives type 2 inflammation.3

Both IL-4 and IL-13 cytokines are key drivers of AD, with unique and complementary roles.6

IL-4
  • IL-4 is required for the differentiation of Th2 cells that contributes to the perpetuation of the type 2 inflammatory cycle in AD3,7
IL-13_IL-4

Both IL-4 and IL-13 contribute to:

  • Skin barrier dysfunction, which weakens the skin barrier and causes increased transepidermal water loss, dryness, and vulnerability to antigens, allergens, pathogens, and other irritants4,6
     
  • The complex mechanisms of acute and chronic itch, including through neuronal sensitization6,8
    • IL-4 and IL-13 affect itch by sensitizing sensory neurons6,8
    • IL-4 also indirectly acts through the production of IL- 31 by Th2 cells4
  • Exacerbating S. aureus colonization which is linked to AD flares6
     
  • Recruiting and activating immune cells in skin tissue, amplifying inflammation4,6
IL-31
  • IL-31 is primarily produced by Th2 cells4
     
  • It activates sensory neurons to induce itch and stimulate cutaneous sensory nerve growth4
    • Sensory nerve sensitization and itch lead to scratching that further exacerbates inflammation and barrier dysfunction4

Type 2 inflammation is driven by multiple cytokines, including IL-4 and IL-13, that play a key role in the pathophysiology of AD.4

ILC2, type 2 innate lymphoid cells.

  1. Kim BE et al. Clin Immunol 2008;126(3):332-337.

  2. Leung DYM, Guttman-Yassky E. J Allergy Clin Immunol 2014;134(4):769-779.

  3. Gandhi NA et al. Nat Rev Drug Discov 2016;15(1):35-50.

  4. Haddad E-B et al. Dermatol Ther (Heidelb) 2022;12(7):1501-1533.

  5. Weidinger S et al. Nat Rev Dis Primers 2018;4(1):1.

  6. Beck LA et al. JID Innov 2022;2(5):100131.

  7. Keegan AD et al. Fac Rev 2021;10:71.

  8. Mack MR et al. Front Mol Neurosci 2023;16:1258823.