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

Written by | Don Candy

Lymph nodes (LNs) are a class of secondary lymphoid organs containing various immune cells that can effectively initiate pathogen-specific adaptive immune responses, and one of the key steps is that they can integrate information from peripheral tissue drainage in lymphatic vessels, including metabolites, cytokines, chemokines, microorganisms or certain forms of pathogens, and different information will shape different immune response qualities to adapt to different peripheral tissues

Unconventional T cells (UTCs) consist of three main clades: γδT cells, MR1 restriction T cells (e.

On August 23, 2022, wolfgang Kastenmuller team from the University of Würzburg in Germany launched a research paper entitled Lymphatic migration of unconventional T cells promotes site-specific immunity in distinct lymph nodes online on Immunity.

To investigate whether LNs in different tissue sites produce a characteristic immune response, the researchers examined three LNs (skin drainage lymph nodes (sdLNs), lung mediastinal lymph nodes (medLNs) and mesenteric lymph nodes (mesLNs)) from mice after stimulation of the culture medium and cytokine response of cells, and found that IL-4 and IL-17 were stronger in sdLNs, and IFNg and IL-17 were stronger

The authors then analyzed the UTCs in these LNs using single-cell sequencing, and the UMAP showed that the UTCs isolated by Thel (encoding CD62L) were separated into two clusters, where the cyclic CD62L+ UTC was characteristically similar in all LNs, while the characteristic composition and transcriptional profiles of the cells of the non-cyclic CD62L- were different

Finally, the researchers studied the spatial location and function of these UTCs, confocal microscopy analyzed tissue sections of sdLNs, and IL-18R/IL-23R double positive cells (representing Th17 polarized UTCs) were found in the subcapsular and interveolar regions, and migrated at a certain rate, with temporary dynamic aggregation after Staphylococcus aureus infection, and no changes

Overall, using LN transplantation, single-cell sequencing, spectral flow cytometry, and fluorescence-reported transgenic mouse models, the researchers elucidated UTCs migrating to localized drainage LNs via lymphatic pathways, each with a unique tissue-determined combination
of UTCs.

Through a single mouse model of UTC deficiency, UTC was found to function in interconnected units, producing a characteristic site-specific immune response
.

Therefore, lymphatic migration of UTCs is a key factor in determining immunity at specific sites in different LNs, and this study has significant implications
for vaccination strategies and immunotherapy methods.

Original address:

https://doi.
org/10.
1016/j.
immuni.
2022.
07.
019

Model Maker: Eleven

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