Lymph node medulla regulates the spatiotemporal unfolding of resident dendritic cell networks

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Immunity. 2023 Aug 8;56(8):1778-1793.e10. doi: 10.1016/j.immuni.2023.06.020. Epub 2023 Jul 17.

Lymph node medulla regulates the spatiotemporal unfolding of resident dendritic cell networks

Milas Ugur, R Jacob Labios, Chloe Fenton, Konrad Knöpper, Katarzyna Jobin, Fabian Imdahl, Gosia Golda, Kathrin Hoh, Anika Grafen, Tsuneyasu Kaisho, Antoine-Emmanuel Saliba, Dominic Grün, Georg Gasteiger, Marc Bajénoff, Wolfgang Kastenmüller

Würzburg Institute of Systems Immunology, Max Planck Research Group at the, Julius-Maximilians-Universität Würzburg, 97078, Würzburg, Germany. Helmholtz Institute for RNA-Based Infection Research (HIRI), Helmholtz Centre for Infection Research (HZI), 97080 Würzburg, Germany. Department of Immunology Institute of Advanced Medicine, Wakayama Medical University, 641-8509 Wakayama, Japan. Aix Marseille Université, CNRS, INSERM, CIML, 13288 Marseille, France.

Service type: Knock-in mice


Unlike macrophage networks composed of long-lived tissue-resident cells within specific niches, conventional dendritic cells (cDCs) that generate a 3D network in lymph nodes (LNs) are short lived and continuously replaced by DC precursors (preDCs) from the bone marrow (BM). Here, we examined whether specific anatomical niches exist within which preDCs differentiate toward immature cDCs. In situ photoconversion and Prtn3-based fate-tracking revealed that the LN medullary cords are preferential entry sites for preDCs, serving as specific differentiation niches. Repopulation and fate-tracking approaches demonstrated that the cDC1 network unfolded from the medulla along the vascular tree toward the paracortex. During inflammation, collective maturation and migration of resident cDC1s to the paracortex created discontinuity in the medullary cDC1 network and temporarily impaired responsiveness. The decrease in local cDC1 density resulted in higher Flt3L availability in the medullary niche, which accelerated cDC1 development to restore the network. Thus, the spatiotemporal development of the cDC1 network is locally regulated in dedicated LN niches via sensing of cDC1 densities.

Keywords: CD135; Flt3L; Prtn3; cDC1; conveyor belt; feedback; infection; inflammation; migration; preDC.

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