Accéder au contenu
Merck

CCL2 and CXCL12 Derived from Mesenchymal Stromal Cells Cooperatively Polarize IL-10+ Tissue Macrophages to Mitigate Gut Injury.

Cell reports (2020-02-13)
Jayeeta Giri, Rahul Das, Emily Nylen, Raghavan Chinnadurai, Jacques Galipeau
RÉSUMÉ

Mesenchymal stromal cell (MSC)-based therapy for inflammatory diseases involves paracrine and efferocytotic activation of immunosuppressive interleukin-10+ (IL-10+) macrophages. The paracrine pathway for MSC-mediated IL-10+ macrophage functionality and response to tissue injury is not fully understood. In our present study, clodronate pre-treatment of colitic mice confirms the essential role of endogenous macrophages in bone-marrow-derived MSC (BM-MSC)-mediated clinical rescue of dextran sulfate sodium (DSS)-induced colitis. We identify that BM-MSC-secreted chemokine ligand 2 (CCL2) and C-X-C motif chemokine 12 (CXCL12) cooperate as a heterodimer to upregulate IL-10 expression in CCR2+ macrophages in vitro and that CCL2 expression by MSC is required for IL-10+ polarization of intestinal and peritoneal resident macrophages in vivo. We observe that tissue macrophage IL-10 polarization in vivo is widespread involving extra-intestinal tissues and secondarily leads to bystander IL-10 expression in intestine-resident B and T cells. In conclusion, the BM-MSC-derived chemokine interactome dictates an IL-10+-macrophage-amplified anti-inflammatory response in toxic colitis.

MATÉRIAUX
Référence du produit
Marque
Description du produit

Sigma-Aldrich
AMD3100 octahydrochloride hydrate, ≥97% (NMR), solid
Sigma-Aldrich
RS 102895 hydrochloride, ≥98% (HPLC), powder
Sigma-Aldrich
MMP-1 human, recombinant, expressed in HEK 293 cells, ≥95% (SDS-PAGE)