Epidermis instructs skin homing receptor expression in human T cells

Area of Science:

• Immunology
• Dermatology
• Cell Biology

Background:

• Memory T cell localization is crucial for skin immunity and barrier function.
• Current models suggest lymph node dendritic cells imprint tissue-specific homing.

Purpose of the Study:

• To investigate the mechanisms controlling memory T cell migration to human skin.
• To identify skin-specific factors that regulate T cell homing.

Main Methods:

• Coculture of naive T cells with primary epidermal keratinocytes.
• Analysis of chemokine receptor (CCR8) and cutaneous lymphocyte-associated antigen (CLTA) expression.
• Comparison with other epithelial cell types (mesothelium, small intestine).

Main Results:

• Skin-derived factors, primarily from keratinocytes, induce CCR8 expression in naive T cells.
• This induction promotes preferential homing of T cells to the skin.
• Keratinocyte-induced CCR8 expression is independent of vitamins A and D.
• CCR8 induction correlates with increased CLTA expression.
• No similar imprinting effect was observed with non-skin epithelial cells.

Conclusions:

• Steady-state epidermis, particularly keratinocytes, plays a key role in directing T cell localization to the skin.
• This finding challenges existing paradigms of T cell homing, particularly those involving CCR10.
• The study highlights a novel mechanism for skin-resident memory T cell generation and maintenance.