C-Reactive Protein Promotes the Expansion of Myeloid Derived Cells With Suppressor Functions

Area of Science:

• Immunology
• Nephrology
• Cell Biology

Background:

• Human C-reactive protein (CRP) exacerbates acute kidney injury in mice.
• This exacerbation is linked to increased myeloid-derived suppressor cells (MDSCs) in the kidneys.

Purpose of the Study:

• To investigate the direct effects of CRP on MDSC development and function in vitro.
• To elucidate the mechanisms underlying CRP's modulation of MDSCs.

Main Methods:

• Bone marrow progenitor cultures from wild-type and FcγRIIB-deficient mice.
• Co-culture assays with MDSCs and T cells.
• Measurement of intracellular reactive oxygen species (iROS) production.
• Assessment of T cell proliferation suppression.

Main Results:

• CRP dose-dependently increased MDSC generation from bone marrow progenitors.
• CRP enhanced MDSC production of iROS in a FcγRIIB-independent manner.
• CRP augmented MDSC-mediated suppression of T cell proliferation, which was FcγRIIB-dependent.
• CRP enabled human neutrophils to suppress autologous T cell proliferation.

Conclusions:

• CRP directly modulates MDSC development and enhances their suppressive functions.
• CRP's effects on MDSC expansion and iROS production are FcγRIIB-independent.
• CRP's enhancement of MDSC suppressive activity is FcγRIIB-dependent.
• CRP may act as an endogenous regulator of MDSC activity in vivo.