Expression of CCR6 and CD83 by cytokine-activated human neutrophils

Area of Science:

• Immunology
• Cell Biology

Background:

• Polymorphonuclear leukocytes (PMNLs) were traditionally considered terminally differentiated and incapable of protein synthesis or T cell interaction.
• The potential for PMNLs to undergo phenotypic and functional changes was largely unexplored.

Purpose of the Study:

• To investigate whether PMNLs can alter their phenotype and function in response to specific immune signals.
• To explore the role of cytokines in inducing changes in PMNLs.

Main Methods:

• Incubation of PMNLs with supernatants from phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PHA-sup).
• Neutralization studies using IgG against various cytokines to identify key inducers.
• Treatment with recombinant cytokines like tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma).
• Analysis of gene expression (CCR6 mRNA) and cell surface marker expression (CD83, CD40, HLA-DR).
• Functional assays including chemokine binding and migration studies.

Main Results:

• PMNLs incubated with PHA-sup expressed high levels of CCR6 mRNA, primarily induced by TNF-alpha.
• Recombinant TNF-alpha and IFN-gamma synergistically increased CCR6 mRNA expression.
• Cytokine-activated PMNLs expressed functional CCR6, demonstrated by LARC binding and migration.
• Activated PMNLs expressed dendritic cell (DC)-like markers, including CD83, CD40, and HLA-DR, depending on the cytokine combination.

Conclusions:

• PMNLs can undergo a differentiation process under specific cytokine stimulation, acquiring phenotypes and functions similar to immature dendritic cells.
• These findings challenge the traditional view of PMNLs as terminally differentiated cells.
• Differentiated PMNLs may possess novel roles in modulating adaptive immune responses.