IADR Abstract Archives
IL-37-Producing and IL-37/IL-35-Coproducing CD138+CD38+Regulatory Plasma Cells in Human Gingival Tissue
Objectives: Distinct sets of CD138+IgM+ regulatory plasma cells (Preg) exist and are involved in the production of anti-inflammatory (e.g., IL-10 and IL-35) and pro-inflammatory (e.g., IL-17 and TNF-α) cytokines. Plasma cells represent ~50% of the infiltrated immune cells in chronic periodontitis (CP) lesions; however, the presence of Preg in CP is unknown. This study sought to identify the infiltration of Preg cells in human gingival tissue of CP subjects, and investigate the role of IL-37 and IL-35 in osteoclast differentiation.
Methods: The localization of CD138, CD38, IL-37 and IL-35 was determined by immunohistochemistry in 5 CP subjects. Co-localization was determined using immunofluorescence and confocal microscopy. The role of IL-37 and IL-35 in osteoclast differentiation was assessed using an in vitro osteoclast differentiation system (Bone Marrow Derived Macrophages) supplemented with recombinant human IL-37 and IL-35 at various dosages. Osteoclasts were detected with Tartrate-resistant acid phosphatase (TRAP) cell staining. Differences in osteoclast numbers were tested using ANOVA and a p<0.05 statistical significance threshold.
Results: We discovered two new subsets of CD138+CD38+ regulatory plasma cells in human CP gingival tissue. The first subset of Preg [denoted as “IL-37 producing Preg” (CD138+CD38+ i37-Preg)] robustly produces IL-37, has high cytoplasmic staining of IL-37. The second subset of Preg (CD138+CD38+ i37/i35-Preg) coproduces IL-37 and IL-35. Both subsets are IgG+ Preg cells. Moreover, both IL-37 and IL-35 exhibited a dose-response inhibition of osteoclast differentiation in vitro (80% inhibition and p <0.05)
Conclusions: We found strong evidence that infiltrated plasma cells in the human gingival tissue of CP patients can express two anti-inflammatory cytokines: IL-37 and IL-35. These data suggest a potential protective role of i37-Preg and i37/i35-Preg in alveolar bone loss in periodontitis. Importantly, our findings highlight possible new therapeutic strategies involving utilization of these two subsets of Preg to suppress bone loss of periodontal disease
Methods: The localization of CD138, CD38, IL-37 and IL-35 was determined by immunohistochemistry in 5 CP subjects. Co-localization was determined using immunofluorescence and confocal microscopy. The role of IL-37 and IL-35 in osteoclast differentiation was assessed using an in vitro osteoclast differentiation system (Bone Marrow Derived Macrophages) supplemented with recombinant human IL-37 and IL-35 at various dosages. Osteoclasts were detected with Tartrate-resistant acid phosphatase (TRAP) cell staining. Differences in osteoclast numbers were tested using ANOVA and a p<0.05 statistical significance threshold.
Results: We discovered two new subsets of CD138+CD38+ regulatory plasma cells in human CP gingival tissue. The first subset of Preg [denoted as “IL-37 producing Preg” (CD138+CD38+ i37-Preg)] robustly produces IL-37, has high cytoplasmic staining of IL-37. The second subset of Preg (CD138+CD38+ i37/i35-Preg) coproduces IL-37 and IL-35. Both subsets are IgG+ Preg cells. Moreover, both IL-37 and IL-35 exhibited a dose-response inhibition of osteoclast differentiation in vitro (80% inhibition and p <0.05)
Conclusions: We found strong evidence that infiltrated plasma cells in the human gingival tissue of CP patients can express two anti-inflammatory cytokines: IL-37 and IL-35. These data suggest a potential protective role of i37-Preg and i37/i35-Preg in alveolar bone loss in periodontitis. Importantly, our findings highlight possible new therapeutic strategies involving utilization of these two subsets of Preg to suppress bone loss of periodontal disease