A Positive Feedback Loop Between Th17 Cells and Dendritic Cells in Patients with Endplate Inflammation

ABSTRACT

Background: Endplate inflammation remains a difficult disease to treat, in part due to its unclear pathology. Previous experiments showed that patients with idiopathic inflammation presented a systemic upregulation of Th17 cells. Here, we investigated how this change might affect the inflammatory environment in endplate inflammation.

Methods: Peripheral blood was obtained from patients and healthy controls, and Th17 cells were examined.Results: Th17 cells significantly increased the differentiation of CD11c+ and DC-SIGN+ dendritic cells (DCs) from circulating monocytes in the absence of exogenous stimulation as well as in the presence of LPS stimulation. Th17 cells also increased CD80 and CD86 expression by DCs. Importantly, although Th17 cells from both healthy controls and patients with endplate inflammation could induce CD11c, DC-SIGN, CD80, and CD86 expression, Th17 cells from patients with endplate inflammation showed significantly more potent capacity. Both contact-dependent and IL-17-dependent mechanisms were employed by Th17 cells, since blocking cell-to-cell contact significantly inhibited Th17-mediated differentiation of CD11c+ DCs, and neutralization of IL-17 reduced the expression of CD80 and CD86. Strikingly, DCs following incubation with Th17 cells, but not the DCs derived directly from monocytes without Th17 cells, could significantly promote the expression of IL-17 from naive CD4+ T cells.

Conclusions: These results demonstrated that Th17 cells from patients with endplate inflammation could potently induce the differentiation and activation of DCs that preferentially promoted IL-17 response in a positive feedback loop.

KEYWORDS:

• CD4+ T cell
• Dendritic cell
• Endplate inflammation
• Th17 cell

Acknowledgments

This work was supported by the Academic Leader Program of Pudong New Area Commission of Health and Family Planning (PWRd2017-08); the Science and Technology Development Funding of Pudong New Area (PKJ2017-Y33).

Conflict of interest

None.

Additional information

Funding

This work was supported by the Academic Leader Program of Pudong New Area Commission of Health and Family Planning [PWRd2017-08]; the Science and Technology Development Funding of Pudong New Area [PKJ2017-Y33].