Biological clock dysfunction exacerbates contact hypersensitivity in mice

Area of Science:

• Immunology
• Chronobiology
• Dermatology

Background:

• Immediate-type skin allergic reactions are linked to circadian rhythms.
• The influence of circadian mechanisms on delayed-type skin allergic reactions, like contact hypersensitivity (CHS), is not well understood.
• CHS is a T-cell-mediated immune response and a model for allergic contact dermatitis.

Purpose of the Study:

• To investigate the impact of biological clock dysfunction on CHS pathogenesis.
• To compare CHS in CLOCK mutant mice with wild-type (WT) mice.

Main Methods:

• Mice were sensitized with 2,4,6-trinitro-1-chlorobenzene (TNCB) on the abdomen.
• Mice were challenged with TNCB on the ears to induce CHS.
• Evaluated ear swelling, serum immunoglobulin E, mast cell numbers, and corticosterone levels.

Main Results:

• CLOCK mutant mice exhibited more severe inflammation, increased ear swelling, higher serum immunoglobulin E, and more mast cells compared to WT mice.
• Biological clock dysfunction promoted T-helper type 2 immune responses, exacerbating CHS.
• CLOCK mutation led to loss of corticosterone rhythmicity and decreased daily levels, worsening CHS. Adrenalectomy exacerbated CHS in WT mice but not CLOCK mutant mice. Dexamethasone offered greater protection in CLOCK mutant mice.

Conclusions:

• Circadian rhythm plays a significant role in regulating CHS.
• Corticosterone rhythmicity and levels are implicated in the circadian regulation of CHS.
• CLOCK mutation disrupts corticosterone regulation, leading to exacerbated CHS.