IL-23-producing CD68(+) macrophage-like cells predominate within an IL-17-polarized infiltrate in chronic periodontitis lesions

Abstract

Aim: To analyse antigen-presenting cells (APCs), such as dendritic cells (DCs), macrophages (Mo) or B cells depending on the regional site of chronic periodontitis (CP), and to investigate their relation to Th17 cells.

Material and methods: Biopsies from oral mucosa as well as the coronal and bottom regions of CP were analysed by immunhistochemistry, immunofluorescence, flow cytometry and real-time PCR.

Results: A predominance of CD68(+) Mo-like cells and CD20(+) B cells and strong Th17 infiltration was observed in the bottom region of CP lesions, while CD1a(+) DCs were only detected in the coronal regions, where Th17 infiltration was low. Furthermore, CD68(+) Mo-like cells displayed CD163 expression as a typical Mo-marker, but expressed in parallel typical DCs markers, such as CD11c or CD209 and TLR4. Interestingly, Th17-inducing cytokine IL-23p19 was produced by CD68(+) Mo-like cells, but not CD20(+) B cells. Moreover, the stimulation of in vitro generated CD68(+) Mo-like cells by Porphyromonas gingivalis-derived (Pg) lipopolysaccharide resulted in the upregulation of their IL-23p19 mRNA expression, which was inhibited by the blockage of TLR4.

Conclusions: In view of these data, a picture emerges that IL-17-producing cells in CP could be in part directed by CD68(+) Mo-like cells, which produce IL-23p19 upon TLR4 activation by Pg.