IL-38 orchestrates proliferation and differentiation in human keratinocytes

Area of Science:

• Dermatology
• Immunology
• Cell Biology

Background:

• Interleukin (IL)-38 is part of the IL-1 cytokine family, known for anti-inflammatory properties.
• IL-38 is predominantly expressed in the skin by differentiating keratinocytes, but its specific functions remain largely uncharacterized.

Purpose of the Study:

• To investigate the biological functions of IL-38 in skin physiology.
• To determine the role of IL-38 in keratinocyte differentiation, proliferation, and its involvement in skin pathologies.

Main Methods:

• Utilized two- and three-dimensional cell cultures to study keratinocyte behavior.
• Performed immunohistochemical analysis on skin tissues.
• Investigated the intracellular localization and effects of IL-38 overexpression on transcription regulators.

Main Results:

• IL-38 is expressed not only by keratinocytes but also by dermal fibroblasts and skin appendage epithelial cells.
• Endogenous IL-38 expression positively correlates with keratinocyte differentiation.
• Overexpression of IL-38 inhibited keratinocyte proliferation and enhanced differentiation.
• IL-38 was downregulated in hyperproliferative skin conditions like psoriasis and skin cancers.
• IL-38 shuttles between the nucleus and cytoplasm, modulating YAP and ID1 activity.

Conclusions:

• IL-38 directly influences epidermal homeostasis by regulating keratinocyte proliferation and differentiation, independent of immune system activation.
• Downregulation of IL-38 is associated with skin pathologies involving keratinocyte hyperproliferation.
• Keratinocyte-derived IL-38 is crucial for maintaining skin health and may be a therapeutic target for epidermal alterations.