Inflammation by immune cells has profound effects on the destruction or regeneration of dental tissues, including jaw bones, periodontium and teeth. Consequently, understanding the interplay between immune cells and dental tissues has become a critical issue in dentistry. In the oral/maxillofacial area, there are more than 300 cervical lymph-nodes (LNs) where inflammatory responses by immune cells are coordinated. Conventionally, enlarged cervical LNs are considered as faithful markers of immune activation by infection or tumor metastasis, but if other factors can also contribute to cervical lymphadenopathy is unknown. Using various mouse models of genetic deficiencies, here we aimed to identify potential mechanisms of lymphadenopathy in the oral/maxillofacial area.
Method:
To assess LN development and distribution, mice were subjected to whole-body MRI followed by detailed necropsy. Isolated LNs were further analyzed by immunohistochemistry or processed to single cell suspensions to assess lymphocyte contents. LN cells were phenotyped by surface staining using a series of lineage and activation markers using flow cytometry. Cell viability was examined by TUNEL assay and caspase-3 analysis.
Result:
Gfi1 is a transcription factor involved in diverse biological processes such as inner ear hair cell development and neutrophil differentiation. Here we report that Gfi1 also controls LN development and induces lymphadenopathy, however, exclusively in the cervical area. In Gfi1-deficient mice, mandibular and jugular LNs were dramatically enlarged, but importantly without any evidence of local infection or tumor. In histological sections and flow cytometry, Gfi1-deficient LNs showed lymphocyte hyperplasia with increased frequency of a non-B, non-T cell population, and no effect on Foxp3+ regulatory CD4 T cells.
Conclusion:
Here we report for the first time a genetic basis for cervical LN enlargement. Our findings have implications for human diseases with similar phenotypes such as the Kikuchi-Fujimoto disease and underline the possibility of genetic deficiency of such clinical phenotypes.