Characterization of Inflammation-derived CD11c⁺ Dendritic Cells in Mouse Model of Periodontal Disease

Abstract

We have previously shown that Foxp3⁺ CD4⁺ regulatory T (Foxp3⁺ Treg) cells are elevated in inflamed gingival tissues of mice infected with Porphylomonas gingivalis (P. gingivalis), a major periopathologic bacteria. Foxp3⁺ Treg cells play a crucial role in maintaining immune tolerance and homeostasis. In this study, we elucidated the mechanisms ofFoxp3⁺ Treg cell induction at sites ofinflamed gingival tissue. A murine periodontal disease model with alveolar bone loss was established by oral infection with 10⁹ cfu of P. gingivalis suspended in 0.1ml ofPBS with 2% carboxymethylcellulose, 15times over three weeks. Gingival mononuclear cells were isolated from mouse gingival tissues for analysis by kinetic observation. Elevated numbers ofCD11c⁺ dendritic cells (DCs) but low expression ofco-stimulatory (CD40, 80, 86) and MHC-II were detected in inflamed gingival tissues. Interestingly, significantly induction of IL-6 and TGF-β transcripts was detected in early stages ofthe inflammation period. Furthermore, expression levels ofTGF-βtranscripts were maintained through the end ofexperiment. Importantly, diminished levels ofIL-6 transcripts but significant induction ofretinal dehydrogenase 2 (RALDH2) transcripts, a major enzyme for retinoic acid synthesis, were detected in later stages of the inflammation period. These results suggest that inflammation-derived CD11c⁺ DCs regulate inflammation and induce Foxp3⁺ Treg cells in the gingiva ofthe mouse model.