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


ABSTRACT: 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.

SUBMITTER: Giri J 

PROVIDER: S-EPMC7043065 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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

Giri Jayeeta J   Das Rahul R   Nylen Emily E   Chinnadurai Raghavan R   Galipeau Jacques J  

Cell reports 20200201 6


Mesenchymal stromal cell (MSC)-based therapy for inflammatory diseases involves paracrine and efferocytotic activation of immunosuppressive interleukin-10<sup>+</sup> (IL-10<sup>+</sup>) macrophages. The paracrine pathway for MSC-mediated IL-10<sup>+</sup> 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 c  ...[more]

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