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Updated: Jul 27, 2025

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production

Published on: March 2, 2014

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JAK Signaling Is Critically Important in Cytokine-Induced Viral Susceptibility of Keratinocytes

Kimberly A Arnold1, Liam F Peterson2, Lisa A Beck1,2

  • 1Departments of Dermatology, University of Rochester Medical Center, Rochester, NY 14642, USA.

International Journal of Molecular Sciences
|June 10, 2023
PubMed

Insights

Certain immune signaling proteins, like IL-4/IL-13 and IL-22, increase skin cell susceptibility to viruses, while IFNγ offers protection. Janus kinase inhibitors (JAKi) can modulate these effects.

Area of Science:

  • Immunology
  • Dermatology
  • Virology

Background:

  • Keratinocytes (KC) are crucial for skin immunity and barrier function.
  • Type 1 (interferon-gamma, IFNγ), type 2 (interleukin-4/13, IL-4/IL-13), and type 3 (IL-17A/IL-22) cytokines are implicated in skin diseases like atopic dermatitis, psoriasis, and lupus.
  • Janus kinase inhibitors (JAKi) are therapeutic agents for these conditions.

Purpose of the Study:

  • To investigate how type 1, 2, and 3 cytokines affect keratinocyte susceptibility to viral infections.
  • To determine if JAK inhibitors can modulate cytokine-induced changes in viral susceptibility in keratinocytes.

Main Methods:

  • Immortalized and primary human keratinocytes were pretreated with specific cytokines (IFNγ, IL-4/IL-13, IL-22).
  • Cells were subsequently infected with vaccinia virus (VV) or herpes simplex virus-1 (HSV-1).
  • The effect of JAK inhibitors (targeting JAK1, TYK2, or JAK2) on viral infection was assessed.

Main Results:

  • Type 2 (IL-4 + IL-13) and type 3 (IL-22) cytokines significantly increased keratinocyte susceptibility to VV infection.
  • IFNγ significantly reduced keratinocyte susceptibility to VV infection.
  • JAK1 inhibition reversed IL-4/IL-13-induced susceptibility, TYK2 inhibition reversed IL-22-induced susceptibility, and JAK2 inhibition reversed IFNγ-mediated protection.

Conclusions:

  • Cytokines prevalent in atopic dermatitis skin (IL-4, IL-13, IL-22) enhance keratinocyte viral susceptibility.
  • IFNγ exhibits a protective effect against viral infection in keratinocytes.
  • JAK inhibitors demonstrate potential in modulating these cytokine-driven changes in viral susceptibility, offering therapeutic insights for skin diseases.
Keywords:
Janus kinase inhibitorscytokinesimmune profileskeratinocyteviral infection

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