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Lymphatic migration of unconventional T cells promotes site-specific immunity in distinct lymph nodes

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2022

Immunity. 2022 Aug 17;S1074-7613(22)00354-5. doi: 10.1016/j.immuni.2022.07.019. Online ahead of print.

Lymphatic migration of unconventional T cells promotes site-specific immunity in distinct lymph nodes

Marco A Ataide, Konrad Knöpper, Paulina Cruz de Casas, Milas Ugur, Sarah Eickhoff, Mangge Zou, Haroon Shaikh, Apurwa Trivedi, Anika Grafen, Tao Yang, Immo Prinz, Knut Ohlsen, Mercedes Gomez de Agüero, Andreas Beilhack, Jochen Huehn, Mauro Gaya, Antoine-Emmanuel Saliba, Georg Gasteiger, Wolfgang Kastenmüller

Würzburg Institute of Systems Immunology, Max Planck Research Group at the Julius-Maximilians-Universität Würzburg, 97078 Würzburg, Germany. Experimental Immunology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany. Department of Medicine II and Pediatrics, Würzburg University Hospital, ZEMM, 97078 Würzburg, Germany. Centre d'Immunologie de Marseille-Luminy (CIML), Department of Immunology, 13288 Marseille, France. Institute of Immunology, Hannover Medical School, 30625 Hannover, Germany. Institute of Systems Immunology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany. Institute for Molecular Infection Biology (IMIB), 97078 Würzburg, Germany. Experimental Immunology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, 30625 Hannover, Germany. Helmholtz Institute for RNA-Based Infection Research (HIRI), Helmholtz-Center for Infection Research (HZI), 97078 Würzburg, Germany. Würzburg Institute of Systems Immunology, Max Planck Research Group at the Julius-Maximilians-Universität Würzburg, 97078 Würzburg, Germany.

Service type: Knock-in mice

Abstract

Lymphatic transport of molecules and migration of myeloid cells to lymph nodes (LNs) continuously inform lymphocytes on changes in drained tissues. Here, using LN transplantation, single-cell RNA-seq, spectral flow cytometry, and a transgenic mouse model for photolabeling, we showed that tissue-derived unconventional T cells (UTCs) migrate via the lymphatic route to locally draining LNs. As each tissue harbored a distinct spectrum of UTCs with locally adapted differentiation states and distinct T cell receptor repertoires, every draining LN was thus populated by a distinctive tissue-determined mix of these lymphocytes. By making use of single UTC lineage-deficient mouse models, we found that UTCs functionally cooperated in interconnected units and generated and shaped characteristic innate and adaptive immune responses that differed between LNs that drained distinct tissues. Lymphatic migration of UTCs is, therefore, a key determinant of site-specific immunity initiated in distinct LNs with potential implications for vaccination strategies and immunotherapeutic approaches.

Keywords: MAIT cells; NKT cells; UTCs; gd T cells; innate immunity; innate-like T cells; mucosal immunity; niche; scRNA sequencing; tissue immunity.

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