Abstract
Interleukin-31 (IL-31) is a type 2 helper T-cell-derived cytokine that has recently been shown to cause severe inflammation and tissue remodeling in multiple chronic diseases of the skin and lungs. IL-31 is upregulated in allergic and inflammatory diseases, including atopic dermatitis, asthma, cutaneous T-cell lymphomas, and allergic rhinitis, as well as autoimmune diseases such as systemic erythematosus. Overexpression of IL-31 in T cells causes severe inflammation, with histological features similar to skin lesions of patients with atopic dermatitis. However, the molecular mechanisms involved in IL31-driven pathological remodeling in skin diseases remain largely unknown. Here, we studied the role of IL-31 in skin damage as a result of intradermal administration of recombinant IL-31 into mice. Notably, IL-31 was sufficient to increase epidermal basal-cell proliferation and thickening of the epidermal skin layer. Our findings demonstrate a progressive increase in transepidermal water loss with chronic administration of IL-31 into the skin. Further, analysis of the skin transcriptome indicates a significant increase in the transcripts involved in epidermal-cell proliferation, epidermal thickening, and mechanical integrity. In summary, our findings demonstrate an important role for IL-31 signaling in epidermal cell proliferation and thickening that together may lead to impaired skin-barrier function in pathological remodeling of the skin.
Highlights
Interleukin-31 (IL-31) is a recently identified T-cell-derived cytokine that is primarily produced by CD4+ T cells polarized toward a Th2 cytokine profile [1]
Transepidermal water loss (TEWL) was significantly increased in recombinant mouse IL-31 (rIL-31)-treated mice as compared to saline-treated mice on Days 7 and 14 (Fig 2), which suggests that IL-31 contributes to disruption of the skin barrier
To substantiate that epidermal proliferation and differentiation leads to increased TEWL, saline- and rIL-31-treated mouse skin sections were co-immunostained for basal epidermal marker cytokeratin14 and proliferation marker Ki67
Summary
C57BL/6 mice (Jackson Laboratories, Bar Harbor, ME) at 8–14 weeks of age were used for all of the experiments. Mice were housed in the Cincinnati Children’s Hospital Medical Center (CCHMC) animal facility, which is approved by the American Association for the Accreditation of Laboratory Animal Care. All mice were maintained under aseptic conditions and received sterile food and water. Mice were euthanized by intraperitoneal injection of 200 mg/. Experiments were performed following the Institutional Animal Care and Use Committee (IACUC) regulations, and this study was approved by the CCHMC IACUC.
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