4.8 Article

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

Journal

IMMUNITY
Volume 55, Issue 10, Pages 1813-+

Publisher

CELL PRESS
DOI: 10.1016/j.immuni.2022.07.019

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Funding

  1. Core Unit for FACS
  2. Core Unit SysMed of the IZKF Wurzburg
  3. German Research Foundation (DFG) [390874280]
  4. European Research Council (ERC) [819329, 759176]
  5. Max Planck Society (Max Planck Research Groups)
  6. GRK2581 SPHINGOINF''
  7. European Research Council (ERC) [759176, 819329] Funding Source: European Research Council (ERC)

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This study found that tissue-derived unconventional T cells migrate through the lymphatic route to locally draining lymph nodes, resulting in distinct populations of cells in each lymph node. These cells cooperate in immune responses and differ between lymph nodes that drain different tissues.
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.

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