C-reactive protein exacerbates renal ischemia-reperfusion injury: are myeloid derived suppressor cells to blame?

C-reactive protein exacerbates renal ischemia-reperfusion injury: are myeloid derived suppressor cells to blame? Am J Physiol Renal Physiol. 2016 Apr 6;:ajprenal.00107.2016 Authors: Pegues MA, McWilliams IL, Szalai AJ Abstract Myeloid derived suppressor cells (MDSC) are a CD11b(+)Gr1(+)population in mice that can be separated into granulocytic (g-MDSC) and monocytic (m-MDSC) subtypes based on their expression of Ly6G and Ly6C. Both MDSC subtypes are potent suppressors of T cell immunity and their contribution has been investigated in a plethora of diseases including renal cancer, renal transplant, and chronic kidney disease. Whether MDSCs contribute to the pathogenesis of acute kidney injury (AKI) remains unknown. Herein, using human CRP transgenic (CRPtg) and CRP deficient mice (CRP(-/-)) subjected to bilateral renal ischemia-reperfusion injury (IRI), we confirm our earlier finding that CRP exacerbates renal IRI and we show for the first time that this effect is accompanied in CRPtg by a shift in the balance of kidney infiltrating MDSCs towards a suppressive Ly6G(+)Ly6C(low)g-MDSC subtype. In CRPtg, direct depletion of g-MDSCs (using an anti-Gr1 monoclonal antibody) reduced the albuminuria caused by renal IRI, confirming they play a deleterious role. Remarkably, treatment of CRPtg with an antisense oligonucleotide that specifically blocks the human CRP acute phase response also led to a reduction in renal g-MDSC numbers and improved...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research