Lymphatic Migration of Immune Cells

Abstract

Lymphatic vessels collect interstitial fluid that has extravasated from blood vessels and return it to the circulatory system. Another important function of the lymphatic network is to facilitate immune cell migration and antigen transport from the periphery to draining lymph nodes. This migration plays a crucial role in immune surveillance, initiation of immune responses and tolerance. Here we discuss the significance and mechanisms of lymphatic migration of innate and adaptive immune cells in homeostasis, inflammation and cancer.

Keywords: T cells; dendritic cells; lymphatic; migration; neutrophils.

Figure 1

Leukocyte migration from peripheral tissues to draining lymph nodes via afferent lymphatic vessels. Inflammatory cytokines, including IL-1β and TNF-α, produced by tissue-resident myeloid cells, enhance DC and neutrophil migration from tissues to lymphatic vessels. Chemokines, such as CCL21, CX3CL1, and CXCL12, synthesized by LECs in the skin control leukocyte migration to lymphatic vessels and aid transmigration into the vessel lumen. In addition to chemokines, lymphatic endothelial cells produce the lipid S1P, which acts upon S1P receptors, to promote the migration of DCs and T cells into lymphatic vessels and aid trafficking to the draining lymph node. Integrins, such as ICAM-1, CD11b, and LFA-1 may promote leukocyte entry into lymphatic vessels and subsequent migration within lymphatics. Interactions between CD44 and MR promote T cell entry into lymphatic vessels. Lastly, LYVE-1 can bind to hyaluronic acid on DCs, and promote DC entry into lymphatic vessels. ICAM-1, Intercellular Adhesion Molecule 1; LFA-1, lymphocyte function-associated antigen 1; LYVE-1, Lymphatic vessel endothelial hyaluronan receptor 1; MR, macrophage mannose receptor; S1P, sphingosine-1-phosphate.

Figure 2

Neutrophil migration in skin lymphatic vessels. (A) Two-photon microscopy was used to examine the lymphatic migration of neutrophils in response to S. aureus. Images are maximum intensity projections of three-dimensional volumes acquired via two-photon microscopy. Lysozyme M⁺ GFP neutrophil (green) migrating inside a lymphatic vessel (LYVE-1, white) is show at three representative time points. Red track indicates neutrophil's path. Tick marks are 10 μm apart. (B) Two-photon image of a Lysozyme M reporter mouse skin with a Lysozyme M⁺ (green) neutrophil containing S. aureus (red) inside the LYVE-1⁺ lymphatic vessel (white). Scale bar is 10 μm. Figure was adapted from Hampton et al. (6).