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IL-4 and IL-13 signaling mediate inflammation and
barrier dysfunction in atopic dermatitis1-4

and microbes

  • Inducing IL-31, a pruritic cytokine
  • Pro-inflammatory cytokine and chemokine signaling
  • Inflammatory cell recruitment
  • Sensitivity to antigens
  • Inappropriate IgE class switching
  • Epidermal barrier function
  • Antimicrobial proteins
  • Keratinocyte differentiation
  • Epidermal lipids
IL-4 and IL-13 are key upstream mediators of the Type 2 inflammatory
pathway that modulate multiple downstream mediators—including
IL-5, IL-31, and IgE—setting in motion the chronic underlying
inflammation of atopic dermatitis2-6

Increased IL-4 and IL-13 signaling drives Type 2 inflammation and
contributes to clinical disease features in atopic dermatitis7-11

IL-4 promotes Th2 differentiation, perpetuating the Type 2 inflammatory cascade

Increased IL-4 and IL-13 signaling contributes to disease features such as:

  • Barrier dysfunction
  • Susceptibility to skin infection
  • Chronic itch

ILC2, type 2 innate lymphoid cells.

References: 1. Brandt EB, Sivaprasad U. Th2 cytokines and atopic dermatitis. J Clin Cell Immunol. 2011;2(3):110. doi:10.4172/2155-9899.1000110 2. Gittler JK, Shemer A, Suárez-Fariñas M, et al. Progressive activation of TH2/TH22 cytokines and selective epidermal proteins characterizes acute and chronic atopic dermatitis. J Allergy Clin Immunol. 2012;130(6):1344-1354. 3. Guttman-Yassky E, Nograles KE, Krueger JG. Contrasting pathogenesis of atopic dermatitis and psoriasis—part II: immune cell subsets and therapeutic concepts. J Allergy Clin Immunol. 2011;127(6):1420-1432. 4. Noda S, Krueger JG, Guttman-Yassky E. The translational revolution and use of biologics in patients with inflammatory skin diseases. J Allergy Clin Immunol. 2015;135(2):324-336. 5. Guttman-Yassky E, Dhingra N, Leung DYM. New era of biologic therapeutics in atopic dermatitis. Expert Opin Biol Ther. 2013;13(4):549-561. 6. Biedermann T, Skabytska Y, Kaesler S, Volz T. Regulation of T cell immunity in atopic dermatitis by microbes: the yin and yang of cutaneous inflammation. Front Immunol. 2015;6:353. doi:10.3389/fimmu.2015.00353 7. Palomares O, Akdis M, Martín-Fontecha M, Akdis CA. Mechanisms of immune regulation in allergic diseases: the role of regulatory T and B cells. Immunol Rev. 2017;278(1):219-236. 8. Weidinger S, Beck LA, Bieber T, Kabashima K, Irvine AD. Atopic dermatitis. Nat Rev Dis Primers. 2018;4(1):1. doi:10.1038/s41572-018-0001-z 9. Rerknimitr P, Otsuka A, Nakashima C, Kabashima K. The etiopathogenesis of atopic dermatitis: barrier disruption, immunological derangement, and pruritus. Inflamm Regen. 2017;37:14. doi:10.1186/s41232-017-0044-7 10. Brunner PM, Guttman-Yassky E, Leung DYM. The immunology of atopic dermatitis and its reversibility with broad-spectrum and targeted therapies. J Allergy Clin Immunol. 2017;139(4):S65-S76. 11. Gandhi NA, Bennett BL, Graham NMH, Pirozzi G, Stahl N, Yancopoulos GD. Targeting key proximal drivers of type 2 inflammation in disease. Nat Rev Drug Discov. 2016;15(1):35-50.