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Sang-Mok Lee, William Stevenson, Kishore Reddy Katikireddy, Hyun Soo Lee, Thomas Dohlman, Sunil Chauhan, Jing Hua, Zahra Sadrai, Masahiro Omoto, Reza Dana; The Effect of Trigeminal Neurons on the Expression of Maturation Markers by Bone Marrow-Derived Dendritic Cells. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2054.
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The immune system interacts with the nervous system in a variety of settings. For example, several neuropeptides have been shown to exert immunomodulatory effects on antigen-presenting cells including dendritic cells (DCs). The present study investigated whether or not cultivated trigeminal neurons (TGNs), which provide sensory innervation to the ocular surface, can affect the expression of maturation markers by cultivated bone marrow-derived dendritic cells (BMDCs).
Bone marrow and trigeminal ganglions were harvested from C57BL/6 mice of 6-8 weeks age. After excluding red blood cells, bone marrow cells were cultured in the presence of granulocyte/macrophage colony-stimulating factor (GM-CSF, 20ng/ml) for 6 days to proliferate immature DCs. Loosely-adherent immature DCs were collected and sub-cultured for 2 days in the presence of IFN-γ (10ng/ml) without GM-CSF to induce maturation. Primary cultured TGN or culture supernatants were added to IFN-γ-stimulated BMDCs to evaluate their effects on DC maturation. The expression levels of MHC class II (mouse IA/IE) and CD86 on CD11c+ DCs were analyzed using flow cytometry.
The addition of either TGN or culture supernatant significantly suppressed the expression of MHC class II by IFN-γ-stimulated BMDC compared to IFN-γ-stimulated BMDCs without TGN or their supernatants (control group) (relative frequencies: 79.64 ± 5.24% for control group, 45.55 ± 7.55% for TGN group (P ≤ 0.05), and 63.68 ± 4.86% for supernatant group (P ≤ 0.05), respectively; MFI: 31.72 ± 3.77 for control group, 19.38 ± 2.29 for TGN group (P ≤ 0.05), and 24.48 ± 0.87 for supernatant group (P ≤ 0.05), respectively, Mann-Whitney U test). The cell-surface expression of CD86, a co-stimulatory molecule, demonstrated similar changes to MHC class II expression as a result of TGN co-culture.
Cultivated TGN or their secreted factors are capable of suppressing dendritic cell maturation.
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