Bidirectional homing of Tregs between the skin and lymph nodes

Abstract

Although several homing receptors are known to be differentially expressed by Tregs in lymphoid tissues compared with those found in peripheral tissues, it remains unclear whether these cells traffic between the two locations. In this issue of the JCI, Tomura et al. report steady-state Treg migration from the skin to draining LNs in mice. Furthermore, they report that not only does skin inflammation exacerbate LN-directed Treg homing, it also triggers reverse circulation of Tregs from LNs to skin, whereby these cells contribute to regulation of the immune response. These results now form a new framework for our understanding of Treg homing.

Figure 1. The Kaede (Japanese maple) leaf changes color seasonally.

(A) During summer, the leaf is green due to the presence of chlorophyll. (B and C) In the fall, protease-dependent degradation of chlorophyll and de novo synthesis of anthocyanins turn the leaf red.

Figure 2. Treg trafficking between the skin and draining LNs.

In their study in this issue of the JCI, Tomura et al. used mice expressing the photoconvertible Kaede protein to directly track Treg migration between the skin and LNs in the steady state (A) and during DNFB-induced allergic contact dermatitis (B and C) (17). (A) Upon photoconversion from green to red of skin-resident cells, Kaede-red CD4⁺Foxp3⁺Tregs and Kaede-red CD11c⁺ DCs became detectable in draining LNs, representing steady-state homing of Tregs and DCs from the skin to LNs. They presumably migrate through afferent lymphatic vessels. (B) DNFB-induced allergic contact dermatitis lesions contained increased numbers of Foxp3⁺ Tregs. An even more striking increase was observed in the numbers of Kaede-red Foxp3⁺ Tregs in the draining LNs, demonstrating accelerated Treg homing from inflamed skin. (C) Upon photoconversion of LN-resident cells, Kaede-red Foxp3⁺ Tregs became detectable in the DNFB-induced allergic contact dermatitis lesions. They presumably achieve this reverse migration by moving through efferent LVs, the thoracic duct, and blood vessels.