IRE1α regulates ROS and immune responses after UVB irradiation

Area of Science:

• Skin biology
• Molecular mechanisms of UV damage
• Oxidative stress and inflammation

Background:

• UVB irradiation causes skin damage by generating reactive oxygen species (ROS).
• The unfolded protein response (UPR) is activated to mitigate UVB-induced damage.
• IRE1α is a key mediator within the UPR pathway.

Purpose of the Study:

• To investigate the role of IRE1α in the antioxidant and immune response to UVB irradiation in mouse skin and keratinocytes.
• To understand how IRE1α influences ROS levels and downstream signaling pathways after UV exposure.

Main Methods:

• Utilized mice with epidermal-specific deletion of IRE1α and primary mouse keratinocytes.
• Examined antioxidant response parameters, ROS levels, and immune cell recruitment following UVB irradiation.
• Assessed expression of pro-inflammatory cytokines and keratinocyte proliferation.

Main Results:

• Loss of IRE1α impaired PERK activity and NRF2-dependent antioxidant gene expression.
• IRE1α-deficient keratinocytes showed altered basal and UVB-induced ROS levels.
• Reduced immune cell infiltration and pro-inflammatory cytokine expression were observed in mice lacking IRE1α after UVB exposure.
• Keratinocyte proliferation was diminished following chronic UVB exposure in IRE1α-deficient mice.

Conclusions:

• IRE1α is essential for managing basal and UVB-induced oxidative stress.
• IRE1α plays a critical role in UV-induced skin immune responses and keratinocyte proliferation.
• These findings highlight IRE1α's protective function against UV damage.