IL-4 absence triggers distinct pathways in apical periodontitis development

Abstract

Dental pulp is a specialized tissue able to respond to infectious processes. Nevertheless, infection progress and root canal colonization trigger an immune-inflammatory response in tooth-surrounding tissues, leading to apical periodontitis and bone tissue destruction, further contributing to tooth loss. In order to shed some light on the effects of IL-4 on periradicular pathology development modulation, microtomographic, histological and proteomic analyses were performed using 60 mice, 30 wild type and 30 IL-4−/−. For that, 5 animals were used for microtomographic and histological analysis, and another 5 for proteomic analysis for 0, 7 and 21 days with/without pulp exposure. The periapical lesions were established in WT and IL-4−/− mice without statistical differences in their volume, and the value of p < 0.05 was adopted as significant in microtomographic and histological analyses. Regarding histological analysis, IL-4−/− mice show aggravation of pulp inflammation compared to WT. By using proteomic analysis, we have identified 32 proteins with increased abundance and 218 proteins with decreased abundance in WT animals after 21 days of pulp exposure, compared to IL-4−/− animals. However, IL-4−/− mice demonstrated faster development of apical periodontitis. These animals developed a compensatory mechanism to overcome IL-4 absence, putatively based on the identification of upregulated proteins related to immune system signaling pathways.Significance: IL-4 might play a protective role in diseases involving bone destruction and its activity may contribute to host protection, mainly due to its antiosteoclastogenic action.