GM-CSF induces bone marrow precursors of NOD mice to skew into tolerogenic dendritic cells that protect against diabetes.
We have reported that GM-CSF treatment of NOD mice suppressed diabetes by increasing the number of tolerogenic dendritic cells (tDCs) and Tregs in the periphery. Here, we have investigated whether GM-CSF acted on NOD bone marrow DCs precursors to skew their differentiation to tDCs. DCs were generated from the bone marrow of GM-CSF-treated (GM.BMDCs) and PBS-treated (PBS.BMDCs) NOD mice and were assessed for their ability to acquire tolerogenic properties. Upon LPS stimulation, GM.BMDCs became fully mature, expressed high levels of PD-L1 and produced more IL-10 and less IL-12p70 and IFN-gamma than PBS.BMDCs. In addition, LPS-stimulated GM.BMDCs possessed a reduced capacity to activate diabetogenic CD8(+) T cells in a PD-1/PD-L1-dependent manner. A single injection of LPS-stimulated GM.BMDCs in NOD mice resulted in long-term protection from diabetes, in contrast to LPS-stimulated PBS.BMDCs. Our results showed that GM-CSF-treatment acted on bone marrow precursors to skew their differentiation into tDCs that protected NOD mice against diabetes.
Gaudreau
Simon
S
Department of Pediatrics, Immunology Division, Faculty of Medicine and Health Sciences, University of Sherbrooke, 3001, 12th Avenue North, Sherbrooke, Quebec, Canada J1H 5N4.
Guindi
Chantal
C
Ménard
Michaël
M
Benabdallah
Ahmed
A
Dupuis
Gilles
G
Amrani
Abdelaziz
A
D019264:Adoptive Transfer; D000818:Animals; D018122:B7-1 Antigen / Q000276:immunology; D060890:B7-H1 Antigen; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D003920:Diabetes Mellitus / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D005434:Flow Cytometry; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006651:Histocytochemistry; D007108:Immune Tolerance / Q000276:immunology*; D007371:Interferon-gamma / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D018664:Interleukin-12 / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D010455:Peptides / Q000276:immunology; D013047:Specific Pathogen-Free Organisms
D018122:B7-1 Antigen; D060890:B7-H1 Antigen; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; D010455:Peptides; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor