LILRA5 Functions to Induce ROS Production on Innate Immune Cells

Area of Science:

• Immunology
• Cell Biology
• Molecular Biology

Background:

• Immune receptors on phagocytes are crucial for microbial killing.
• Leukocyte immunoglobulin-like receptor A5 (LILRA5) is an orphan receptor on human phagocytes, poorly characterized.
• LILRA5 co-localizes with FcRγ.

Purpose of the Study:

• To characterize the function and regulation of LILRA5.
• To investigate LILRA5's role in immune responses, particularly in infection and sepsis.

Main Methods:

• Development of a specific agonistic anti-LILRA5 monoclonal antibody.
• Analysis of LILRA5 expression on monocytes and neutrophils.
• Measurement of ROS production upon LILRA5 ligation.
• Assessment of LILRA5 levels in patients with sepsis and systemic infection.
• Investigation of LILRA5 regulation by LPS stimulation and its shedding.

Main Results:

• LILRA5 is expressed on naïve monocytes and neutrophils and stimulates ROS production upon ligation.
• Increased LILRA5 transcripts and soluble LILRA5 (sLILRA5) were observed in sepsis patients.
• LPS stimulation dynamically altered surface LILRA5 expression, suggesting post-transcriptional regulation.
• Shedding of LILRA5 contributes to soluble forms and regulates surface expression.
• Altered surface LILRA5 expression impacts ROS production capacity.

Conclusions:

• LILRA5 is a dynamically regulated activating receptor on phagocytes.
• LILRA5 activation stimulates ROS production, a key microbicidal mechanism.
• LILRA5 regulation via shedding and dynamic expression suggests a role in modulating immune responses during infection.