Circadian clocks guide dendritic cells into skin lymphatics

• Migration of leukocytes from the skin to lymph nodes (LNs) via afferent lymphatic vessels is pivotal for adaptive immune responses.

• Steady-state migration of dermal dendritic cells (DCs) into afferent lymphatic vessels (LVs) is tightly regulated by a variety of promigratory factors.

• In LNs, ~24-h-long circadian rhythms influence the homing capacity and function of lymphocytes; however, whether the draining of leukocytes from tissues occurs in a rhythmic manner is unknown.

• Researchers demonstrate that DCs have a circadian migration pattern into LVs, which peaks during the rest phase in mice. This migration pattern is determined by rhythmic gradients in the expression of the chemokine CCL21 and of adhesion molecules in both mice and humans.

• Chronopharmacological targeting of the involved factors abrogates circadian migration of DCs.

• Researchers identify cell-intrinsic circadian oscillations in skin lymphatic endothelial cells and DCs that cogovern these rhythms, as their genetic disruption in either cell type ablates circadian trafficking.

• These observations indicate that circadian clocks control the infiltration of DCs into skin lymphatics, a process that is essential for many adaptive immune responses and relevant for vaccination and immunotherapies.

Published: 18 October 2021

source:

https://www.nature.com/articles/s41590-021-01040-x

https://doi.org/10.1038/s41590-021-01040-x