Suppression of experimental autoimmune myasthenia gravis by granulocyte-macrophage colony-stimulating factor is associated with an expansion of FoxP3+ regulatory T cells.
Dendritic cells (DCs) have the potential to activate or tolerize T cells in an Ag-specific manner. Although the precise mechanism that determines whether DCs exhibit tolerogenic or immunogenic functions has not been precisely elucidated, growing evidence suggests that DC function is largely dependent on differentiation status, which can be manipulated using various growth factors. In this study, we investigated the effects of mobilization of specific DC subsets-using GM-CSF and fms-like tyrosine kinase receptor 3-ligand (Flt3-L)-on the susceptibility to induction of experimental autoimmune myasthenia gravis (EAMG). We administered GM-CSF or Flt3-L to C57BL/6 mice before immunization with acetylcholine receptor (AChR) and observed the effect on the frequency and severity of EAMG development. Compared with AChR-immunized controls, mice treated with Flt3-L before immunization developed EAMG at an accelerated pace initially, but disease frequency and severity was comparable at the end of the observation period. In contrast, GM-CSF administered before immunization exerted a sustained suppressive effect against the induction of EAMG. This suppression was associated with lowered serum autoantibody levels, reduced T cell proliferative responses to AChR, and an expansion in the population of FoxP3+ regulatory T cells. These results highlight the potential of manipulating DCs to expand regulatory T cells for the control of autoimmune diseases such as MG.
Sheng
Jian Rong
JR
Department of Neurology and Rehabilitation, University of Illinois, Chicago, IL 60612, USA.
Li
Liangcheng
L
Ganesh
Balaji B
BB
Vasu
Chenthamarakshan
C
Prabhakar
Bellur S
BS
Meriggioli
Matthew N
MN
D000818:Animals; D001327:Autoimmune Diseases / Q000628:therapy; D002450:Cell Communication / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology; D051858:Forkhead Transcription Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage / Q000494:pharmacology*; D007114:Immunization; D008565:Membrane Proteins / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D020720:Myasthenia Gravis, Autoimmune, Experimental / Q000276:immunology / Q000517:prevention & control* / Q000628:therapy; D011950:Receptors, Cholinergic / Q000008:administration & dosage / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology*
D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D008565:Membrane Proteins; D011950:Receptors, Cholinergic; C084881:flt3 ligand protein; D016178:Granulocyte-Macrophage Colony-Stimulating Factor