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CS1 (SLAMF7) inhibits production of proinflammatory cytokines by activated monocytes
Jong R Kim1, Nathan C Horton, Stephen O Mathew
1Department of Molecular Biology and Immunology and Institute for Cancer Research, University of North Texas Health Science Center at Fort Worth, TX 76107-2699, USA.
Objective And Design:
CS1 (CRACC, CD319, SLAMF7) is a member of the Signaling Lymphocyte Activation Molecule family expressed on immune cells mediating host defense. CS1 is a self-ligand and has both activating and inhibitory functions in Natural Killer cells. However, the function of CS1 in human monocytes is currently unknown. The objective of this study was to evaluate the control of CS1 surface expression in activated monocytes and to assess the effect of CS1 triggering on proinflammatory cytokine production by monocytes.
Material, Methods And Treatment:
Human monocytes were isolated from PBMC of healthy volunteers by magnetic depletion method or FACS sorting. The monocytes were cultured with or without LPS (1 μg/ml) in the presence or absence of various pharmacological inhibitors to inhibit NF-кB and PI3K signaling pathways. The cells were stimulated with anti-CS1 antibody or isotype control. Total RNA was extracted and RT-PCR was performed using specific primers for CS1 and EAT-2. Cell supernatants were collected and cytokine levels (TNF-α and IL-12p70) were determined by sandwich ELISA.
Results:
Our study revealed that adherent or LPS-activated monocytes express CS1, and CS1 induction is via NF-кB and PI3K pathways. Importantly, cross-linking CS1 resulted in reduced production of proinflammatory cytokines TNF-α and IL-12p70 by LPS-activated monocytes.
Conclusions:
Our study demonstrated that CS1 plays an inhibitory role in human monocytes to control proinflammatory immune responses.
Insights
Signaling Lymphocyte Activation Molecule family member CS1 (CRACC, CD319, SLAMF7) inhibits proinflammatory cytokine production in human monocytes. This discovery reveals CS1
Area of Science:
- Immunology
- Cell Biology
Background:
- CS1 (CRACC, CD319, SLAMF7) is a Signaling Lymphocyte Activation Molecule family member expressed on immune cells.
- CS1 has known roles in Natural Killer cells but its function in human monocytes is unexplored.
Purpose of the Study:
- To investigate the regulation of CS1 surface expression in activated human monocytes.
- To determine the impact of CS1 triggering on monocyte-derived proinflammatory cytokine production.
Main Methods:
- Human monocytes isolated from peripheral blood mononuclear cells (PBMC).
- Monocytes cultured with lipopolysaccharide (LPS) and treated with inhibitors of NF-κB and PI3K pathways.
- CS1 cross-linking performed using anti-CS1 antibody; cytokine levels (TNF-α, IL-12p70) measured via ELISA.
Main Results:
- Adherent and LPS-activated monocytes express CS1, with induction dependent on NF-κB and PI3K signaling.
- Cross-linking CS1 significantly reduced the production of TNF-α and IL-12p70 by LPS-activated monocytes.
Conclusions:
- CS1 exerts an inhibitory function in human monocytes.
- CS1 plays a role in modulating and controlling proinflammatory immune responses.
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