Human CD99L2 Regulates a Unique Step in Leukocyte Transmigration.

Area of Science:

• Immunology
• Cell Biology

Background:

• CD99-like 2 (CD99L2) is a type 1 membrane protein vital for leukocyte transendothelial migration (TEM) in mice.
• Previous studies focused on CD99L2's role in murine inflammation, leaving its function in human inflammation and TEM mechanisms unknown.

Purpose of the Study:

• To investigate the role of CD99L2 in human inflammation and elucidate its mechanism in leukocyte TEM.
• To determine if CD99L2 functions similarly to PECAM and CD99 in human endothelial cells and leukocytes.

Main Methods:

• Studied CD99L2 expression on primary human endothelial cells and leukocytes.
• Utilized antibody blockade and genetic knockdown to inhibit CD99L2 function.
• Assessed the impact of CD99L2 inhibition on human neutrophil and monocyte transmigration across endothelial cells.
• Investigated the sequential steps of TEM involving CD99L2, PECAM, and CD99.

Main Results:

• Human CD99L2 is constitutively expressed at endothelial cell borders and on leukocytes, similar to PECAM and CD99.
• Inhibiting CD99L2 significantly reduced human neutrophil and monocyte transmigration.
• CD99L2 regulates a specific step in TEM, acting sequentially between PECAM and CD99.
• CD99L2 facilitates TEM by recruiting the lateral border recycling compartment, downstream of PECAM.

Conclusions:

• Identified a novel functional role for human CD99L2 in leukocyte TEM.
• Elucidated a TEM mechanism for CD99L2 that is distinct from PECAM and CD99.
• CD99L2 represents a potential therapeutic target for inflammatory diseases.