IL-24 promotes atopic dermatitis-like inflammation through driving MRSA-induced allergic responses
image: IL-24, which is expressed in keratinocytes and induced by S. aureus infection, promotes atopic dermatitis-like inflammation by enhancing a type 2 immune response.
Credit: Xinmin Qian, Meiyi Tong, Tianqing Zhang, Qingqing Li, Meng Hua, Nan Zhou, and Wenwen Zeng
The main text of the study details the experiments conducted to understand the role of IL-24 in AD-like conditions. It describes the methods used, including single-cell RNA sequencing, and the animal models employed to mimic AD. The findings indicate that MRSA infection leads to increased IL-24 in keratinocytes, which in turn heightens type 2 immune responses and worsens AD symptoms. The text further explains the signaling pathways involved, particularly the JAK-STAT-IL-33 axis, and discusses the potential of targeting IL-24 for AD treatment.
Key findings from the study include:
- IL-24 Induction by MRSA: IL-24 is significantly induced in keratinocytes upon MRSA infection. This was revealed through single-cell RNA sequencing, showing a distinct immune response characterized by IL-24 upregulation.
- Exacerbation of AD Symptoms: Administration of recombinant IL-24 protein in animal models worsened AD-like pathology. Conversely, genetic deletion of Il24 or Il20rb in keratinocytes alleviated allergic inflammation and reduced AD symptoms.
- IL-24 and IL-33 Production: IL-24 acts through its receptors on keratinocytes to increase IL-33 production. Elevated IL-33 levels further promote type 2 immunity and exacerbate AD-like conditions.
- Therapeutic Potential: Blocking the JAK-STAT signaling pathway with Ruxolitinib reduced IL-33 levels induced by IL-24, indicating a potential therapeutic approach for AD. Specific deletion of Il20rb in keratinocytes also prevented increased IL-33 production.
This study identifies IL-24 as a crucial mediator in the development and exacerbation of AD-like inflammation, particularly in the presence of MRSA colonization. By promoting type 2 immune responses and increasing IL-33 production, IL-24 significantly worsens AD symptoms. The findings suggest that targeting IL-24 or its signaling pathways could offer new therapeutic strategies for managing AD. The research highlights the complex interactions between microbial colonization, skin cell responses, and immune modulation, providing a deeper understanding of AD pathogenesis and potential avenues for intervention. The work entitled “ IL-24 promotes atopic dermatitis-like inflammation through driving MRSA-induced allergic responses” was published on Protein & Cell (published on May. 16, 2024).