Developing thymocytes cue in unique subsets of neurons to support optimal thymic architecture 

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B1031
Abstract ID: 5903

Presenting Author:
Alexandra M Hoyt-Miggelbrink , PhD candidate at Duke Univ.

Abstract:

Peripheral nervous system innervation of various organs has been associated with the development and maintenance of the immune system. Interestingly, various neurological insults including brain tumors, intracranial metastases, and neurotropic infections have been shown to have profound impacts on peripheral immunity, including thymic size and cellularity. Therefore, we sought to determine whether the thymus was directly innervated. Using flow cytometry and confocal microscopy, we identified a population of cells within the thymus that contained both neuronal markers and morphology. Subsets expressed tyrosine hydroxylase, BIII tubulin and/or NeuN, distinguishing them from thymic epithelial cells. These cells do not express AIRE, further highlighting their neuronal identity. Interestingly, a subset of these neurons also express MCH-II, implying a potential role in T cell selection. Neuronal cell bodies and/or axonal processes were identified within the thymus. Using retrograde rabies virus-derived neurotracers, we confirmed axonal connections and the identity of thymic neurons. Finally, both neuronal and epithelial cells were absent in RAG-deficient mice, suggesting a shared differentiation or survival pathway. Both populations could be restored by introducing healthy bone marrow. To summarize, we describe a novel population of neuronal cells within the thymus that interact with developing thymocytes to establish optimal thymic architecture.