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Role of IL-13

Th2 Cytokines, Including IL-13, Drive Inflammation in AD Skin1

In AD skin, overexpression of IL-13 leads to disruption of the skin barrier, increased risk of skin infections, further amplified inflammation, itch—and, in the chronic phase, remodeling and dermal thickening2-9

Chart created by to show how IL-13 drives atopic dermatitis signs and symptoms

IL-4 can also mediate itch, but concentrations of IL-4 in AD skin are relatively low vs IL-13.7,12 

ILC, innate lymphoid cell; TEWL, transepidermal water loss; TSLP, thymic stromal lymphopoietin.

  • IL-13 acts directly on keratinocytes to:
    • Reduce expression of skin barrier proteins and lipids, thereby further disrupting the skin barrier2-4
    • Down-regulate the expression of antimicrobial peptides, and thereby play a role in the dysbiosis of the skin, which is typically characterized by a strong colonization with Staphylococcus aureus and an increased risk of secondary skin infections5
    • Stimulate the secretion of chemokines and cytokines, which attracts more immune cells and amplifies the inflammatory response6
  • IL-13 may stimulate peripheral itch-sensory neurons, activating itch signaling and scratching7
  • IL-13 down-regulates MMP-13 expression in human dermal fibroblasts and may thereby decrease collagen degradation, resulting in fibrosis with excess collagen deposition, as found in the thickened dermis of chronic lichenified AD skin lesions8
  • Chronic itch sensations and associated scratching are components of a dynamic pathological process known as the itch-scratch cycle9
    • Scratching exacerbates itch sensation through damage to the skin barrier, increasing exposure to allergens and microbes that may further amplify the inflammation
    • The epithelial stress response also releases cytokines that activate immune cells to promote inflammation
    • The released cytokines further stimulate peripheral itch-sensory neurons, resulting in itch signaling and further scratching

In AD skin, studies have found IL-13 to be expressed at higher levels than IL-4.13,14

  1. Bieber T. Interleukin-13: targeting an underestimated cytokine in atopic dermatitis. Allergy. 2019. doi:10.1111/all.13954.
  2. Howell MD, Kim BE, Gao P, et al. Cytokine modulation of atopic dermatitis filaggrin skin expression. J Allergy Clin Immunol. 2007;120(1):150-155.
  3. Kim BE, Leung DY, Boguniewicz M, Howell MD. Loricrin and involucrin expression is down-regulated by Th2 cytokines through STAT-6. Clin Immunol. 2008;126(3):332-337.
  4. Berdyshev E, Golvea E, Bronova I, et al. Lipid abnormalities in atopic skin are driven by type 2 cytokines. JCI Insight. 2018;3(4):e98006.
  5. Nomura I, Goleva E, Howell MD, et al. Cytokine milieu of atopic dermatitis, as compared to psoriasis, skin prevents induction of innate immune response genes.
    J Immunol. 2003;171(6):3262-3269.
  6. Purwar R, Werfel T, Wittmann M. IL-13-stimulated human keratinocytes preferentially attract CD4+CCR4+ T cells: possible role in atopic dermatitis. J Invest Dermatol. 2006;126(5):1043-1051.
  7. Oetjen LK, Mack MR, Feng J, et al. Sensory neurons co-opt classical immune signaling pathways to mediate chronic itch. Cell. 2017;171(1):217-228.e13.
  8. Moriya C, Jinnin M, Yamane K, et al. Expression of matrix metalloproteinase-13 is controlled by IL-13 via PI3K/Akt3 and PKC-δ in normal human dermal fibroblasts.
    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.
  10. Bao K, Reinhardt RL. The differential expression of IL‐4 and IL‐13 and its impact on type‐2 immunity. Cytokine. 2015;75(1):25‐37.
  11. Salimi M, Barlow JL, Saunders SP, et al. A role for IL‐25 and IL‐33‐driven type‐2 innate lymphoid cells in atopic dermatitis. J Exp Med. 2013;210(13):2939‐2950.
  12. Tsoi LC, Rodriguez E, Degenhardt F, et al. Atopic dermatitis is an IL-13-dominant disease with greater molecular heterogeneity compared to psoriasis. J Invest Dermatol. 2019;139(7):1480-1489.
  13. Tazawa T, Sugiura H, Sugiura Y, Uehara M. Relative importance of IL-4 and IL-13 in lesional skin of atopic dermatitis. Arch Dermatol Res. 2004;295(11):459-464.
  14. Koppes SA, Brans R, Ljubojevic Hadzavdic S, Frings-Dresen MH, Rustemeyer T, Kezic S. Stratum corneum tape stripping: monitoring of inflammatory mediators in atopic dermatitis patients using topical therapy. Int Arch Allergy Immunol. 2016;170(3):187-193.