Biological functions of CCL21/CCR7 chemokine axis
Chemotaxis of CCL21/CCR7chemokine axis
Chemotaxis is the most important function of
CCL21/CCR7 chemokine axis in
adaptive immunity (Nomiyama et al., 2013). The specific binding of CCL21
to its receptor CCR7 can mediate the homing of DCs and T lymphocytes to
the secondary lymphoid tissues, and guide the directional movement and
aggregation of T cells in the secondary lymphoid. CCL21/CCR7 chemokine
axis can promote the migration of mature DCs from peripheral tissues to
regional lymph nodes, and enhance the phagocytosis of mature DCs to
different antigens (Ruytinx et al., 2018). DCs are a powerful antigen
presenting cell. Immature DCs are highly active, can effectively absorb
and process antigens, and locate the processed antigens to non-lymphoid
tissues. After exposure to active signals, DCs mature and enter
lymphatic tissues. Because CCL21 plays a vital role in the migration and
functional maturation of DCs ( Ruez et al., 2018, Antonelli et al.,
2014). Additionally, CCL21 was highly espressed in lymphatic epithelial
cells, which combined with CCR7 to facilitate the entry of mature DCs
into lymphatic vessels. Mature DCs entering the lymphatic vessels can be
located in the T lymphocyte area under the action of CCL19.
Nevertheless, CCL21 has chemotactic
effect only on mature DCs and has no chemotactic effect on immature DCs.
CCL21 binds to CCR7 expressed on mature DCs, which exerts biological
effects by inducing the mobilization of calcium ions in mature DCs
(Averbeck et al., 2017). Previous studies have reported that the
combination of CCL21 and CCL19 with CCR7 is both different and
competitive. Physiological concentration of CCL21 shows chemotactic
effect on peripheral blood T cells, but CCL19 does not. This is due to
the different affinity of CCL21 and CCL19 with CCR7. In the presence of
CCL21, T cells move away from CCL19 and toward CCL21, which reflects the
competitive relationship between CCL21 and CCL19. However, both of these
ligands can induce the migration of B cells and tumor cells through
different signal transduction (Yu et al., 2015).