IMMUNOLOGY2024™ Conference Recordings-Homeostasis and activation of heterogeneous thymic dendritic cells are differentially regulated by distinct thymocyte subsets

Homeostasis and activation of heterogeneous thymic dendritic cells are differentially regulated by distinct thymocyte subsets

Back to course

Video Transcription

Video Summary

The talk focused on how thymocytes and dendritic cells (DCs) coordinate immune tolerance in the thymus. The speaker first reviewed T cell development in the cortex and medulla, emphasizing that positively selected thymocytes must migrate into the medulla to encounter self-antigens and undergo negative selection or Treg induction. <br /><br />A major finding was that CCR4 appears early after positive selection and drives thymocyte entry into the medulla before CCR7 is expressed, while CCR7 acts later to retain mature single-positive cells there. CCR4 was especially important for early negative selection, whereas CCR7 was more important for later stages. <br /><br />The speaker then shifted to thymic DCs, showing that CCR7 knockout mice unexpectedly have more Tregs because of altered DC subset balance. Single-cell profiling revealed multiple thymic DC subsets, including conventional DC1/2 and activated DC populations. Different subsets had distinct functions: some were especially good at cross-presenting MTEC-derived antigens, while others were better at inducing Tregs. <br /><br />Finally, the talk showed that CD4 and CD8 thymocytes regulate DC homeostasis and activation differently. CD4 cells were linked to DC1 homeostasis and activation, while CD8 cells affected DC2 and plasmacytoid DCs. The proposed mechanisms involved CD40/NF-kappa B and interferon signaling.

Keywords

thymocytes

dendritic cells

immune tolerance

thymus

CCR4

CCR7

Treg induction