EGFR activation confers protections against UV-induced apoptosis in cultured mouse skin dendritic cells

Area of Science:

• Immunology
• Dermatology
• Cell Biology

Background:

• Ultraviolet radiation (UV) is known to induce apoptosis and functional maturation in skin dendritic cells (DCs).
• The precise molecular mechanisms underlying UV-induced DC activation remain incompletely understood.
• Epidermal growth factor receptor (EGFR) has been previously shown to be activated by UVB in keratinocytes.

Purpose of the Study:

• To investigate the molecular mechanisms of DC activation and apoptosis following UV irradiation, with a specific focus on the role of EGFR.
• To determine if UV irradiation induces EGFR activation in mouse skin DCs and monocyte-derived DCs (MoDCs).
• To elucidate the downstream signaling pathways regulated by EGFR in response to UV exposure in DCs.

Main Methods:

• Utilized cultured mouse skin DCs (XS 106 cell line) and mouse monocyte-derived dendritic cells (MoDCs).
• Employed pharmacological inhibition of EGFR tyrosine kinase to assess downstream signaling.
• Compared UV-induced signaling pathway activation in EGFR-/- cells versus wild-type MEF cells.

Main Results:

• UV irradiation was found to induce EGFR activation in cultured mouse skin DCs and MoDCs.
• Inhibition of EGFR tyrosine kinase significantly suppressed UV-induced activation of MAP kinases (ERK, p38, JNK), transcription factors (c-Fos, c-Jun), PI3K/AKT/mTOR/S6K, and NF-kappaB pathways.
• UV-induced LKB1/AMPK pathway activation was also dependent on EGFR trans-activation.
• MAPK, LKB1/AMPK, PI3K/AKT/mTOR/S6K, and NF-kappaB activation were impaired in EGFR-/- cells after UV radiation compared to wild-type cells.

Conclusions:

• UV irradiation triggers multiple signaling pathways in DCs through EGFR trans-activation.
• EGFR activation plays a crucial role in mediating UV-induced DC maturation, apoptosis, and survival.
• EGFR activation appears to confer protection against UV-induced apoptosis in cultured mouse dendritic cells.