Intestinal epithelial cells express CCL25, which binds CCR9 on gut-homing effector T cell CCL25CCR9˜4:°7integrinCCL25bloodvesselLymphocytes homing to the small intestine bind MAdCAM-1 and the chemokine CCL25 on vascular endothelium laminapropriaintestinalepitheliumCCR9MAdCAM-1˜4:°7
Fig. 11.7 Skinand gut-homing T cells use particular combinations of integrins and chemokines to migrate specifically to their target tissues. α4β7 expressed on circulating lymphocytes primed in gut-associated lymphoid tissues initally binds MAdCAM-1 (upper left panel), then uses CCR9 to move along a CCL25 chemokine gradient to traverse the endothelium and migrate to the intestinal epothelium (upper right panel). Similarly, circulating lymphocytes primed in lymph nodes draining the skin bind to the endothelium lining a cutaneous blood vessel by interactions between cutaneous lymphocyte antigen (CLA) and constitutively expressed E-selectin on the endothelial cells (lower left panel). The adhesion is strengthened by an interaction between lymphocyte chemokine receptor CCR4 and the endothelial chemokine CCL17. Once through the endothelium, effector T lymphocytes are attracted to keratinocytes of the epidermis by the chemokine CCL27, which binds to the receptor CCR10 on lymphocytes (lower right panel).
tissues of the small intestine recruits those T cells back to the lamina propria subjacent to the epithelium of the small intestine along a CCL25 gradient (see Fig. 11.7, upper right panel). In contrast, T cells primed in skin-draining lymph nodes preferentially home back to the skin. They are induced to express the adhesion molecule cutaneous lymphocyte antigen (CLA), an isoform of PSGL-1 that differs in its pattern of glycosylation and binds to E-selectin on cutaneous vascular endothelium (see Fig. 11.7, lower panels). CLA-expressing T lymphocytes also express the chemokine receptors CCR4 and CCR10, which bind sequentially the chemokines CCL17 (TARC) and CCL27 (CTACK), respectively, which are present at highest levels in cutaneous blood vessels and the epidermis. Because these tissue-homing chemokines are produced at steady state, they are referred to as homeostatic chemokines. They are analogous to chemokines produced constitutively in lymphoid tissues at steady state, such as CCL19 and CCL21, that direct CCR7-bearing naive T cells along a gradient from the endothelium of HEVs to T-cell zones (Fig. 11.8). Homeostatic chemokines are to be contrasted with inflammatory chemokines, which are elicited in the context of infection to recruit circulating immune cells to sites of inflammation.