Soluble CD93 is an apoptotic cell opsonin recognized by α_x β₂

Area of Science:

• Immunology
• Cell Biology

Background:

• Efferocytosis, the clearance of apoptotic cells, is vital for maintaining tissue homeostasis and preventing inflammatory and autoimmune diseases.
• CD93, a transmembrane glycoprotein, has been linked to efferocytosis, but its precise role and the function of its soluble form remain unclear.

Purpose of the Study:

• To elucidate the mechanism by which CD93 regulates efferocytosis.
• To determine whether soluble CD93 (sCD93) or membrane-bound CD93 mediates efferocytic activity.
• To identify the receptor for sCD93 involved in apoptotic cell clearance.

Main Methods:

• Utilized cell lines, human monocytes, and macrophages to study CD93 function.
• Employed mass spectrometry to identify the receptor for sCD93.
• Performed deletion mutagenesis to map binding domains of sCD93.
• Used knockdown techniques to assess the role of the identified receptor.

Main Results:

• Soluble CD93 (sCD93) specifically opsonizes apoptotic cells, but not microorganisms.
• Membrane-bound CD93 lacks phagocytic, efferocytic, or tethering activity.
• Identified αxβ2 integrin as the receptor for sCD93.
• Demonstrated that sCD93 bridges apoptotic cells to αxβ2 on macrophages, significantly enhancing efferocytosis.

Conclusions:

• Soluble CD93 (sCD93) functions as a novel opsonin for apoptotic cells.
• The C-type lectin-like domain of sCD93 binds apoptotic cells, while EGF-like repeats bind the αxβ2 integrin receptor.
• This sCD93-αxβ2 interaction is critical for efficient efferocytosis by macrophages, highlighting a new pathway for clearing cellular debris and preventing disease.