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Dendritic cells (DCs) are specialized antigen-presenting cells that play a pivotal role in the pathogenesis of periodontitis. The use of animal models to study the role of DCs in periodontitis has been limited by lack of a method for sustained depletion of DCs. Hence, the objectives of this study were to validate the zDC-DTR knockin mouse model of conventional DCs (cDCs) depletion, as well as to investigate whether this depletion could be sustained long enough to induce alveolar bone loss in this model. zDC-DTR mice were treated with different dose regimens of diphtheria toxin (DT) to determine survival rate. A loading DT dose of 20 ng/bw, followed and maintained with doses of 10 ng/bm every 3 days for up to 4 weeks demonstrated 80% survival. Animals were weighed weekly and peripheral blood was obtained to confirm normal neutrophil counts. Five animals per group were euthanized at baseline, 24 h, 1 and 4 weeks. Bone marrow (BM), spleen (SP) and gingival tissue (GT) were harvested, and cells were isolated, separated and stained for Pre-DCs precursors (CD45R(-) MHCH+ CDHc(+) Flt3(+)CD172a(+)) in BM, cDCs (CDHc(+)MHCH(+)CD209(+)) in spleen, and DCs in GT (CD45R(+) MHCH+ CDHc(+) DC-SIGN/CD209(+)). Pre-Cs in BM were significantly depleted at 24 h and depletion maintained for up to 4 weeks, as compared to blank (PBS) controls. Circulating cDCs in spleen demonstrated a non-significant trend to deplete in 1 week with high variability among mice. GT also showed a similar non-significant trend to deplete in 24 h. The zDC-DTR model seems to be viable for evaluating the role of DCs immune homeostasis disruption and alveolar bone loss pathogenesis in response to long-term oral infection. (C) 2017 Elsevier B.V. All rights reserved.

Dendritic cells are a relative rare population of specialized antigen presenting cells that are distributed through most lymphoid and non-lymphoid tissues and play a critical role in linking the innate and adaptive arms of the immune system. The liver contains a heterogeneous population of dendritic cells that may contribute to liver inflammation and fibrosis through a number of mechanisms. This review summarizes current knowledge on the development and characterization of liver dendritic cells and their potential impact on liver fibrosis. This article is part of a Special Issue entitled: Fibrosis: Translation of basic research to human disease. (C) 2013 Elsevier B.V. All rights reserved.