Immune cell trafficking in uterus and early life is dominated by the mucosal addressin MAdCAM-1 in humans

Background & Aims: In adults, binding of mucosal addressin cell adhesion mo lecule 1 (MAdCAM-1) to lymphocyte (alpha (4)beta (7) integrin directs cell trafficking to gut, whereas interaction of peripheral node addressins (PNAd ) with lymphocyte L-selectin targets immune cells to peripheral lymph nodes (PLNs). Because nothing is known about these addressins during human devel opment, we studied the expression and function of MAdCAM-1 (and PNAd for co mparison) in fetuses and children, Methods: Series of human tissue samples obtained from fetuses (7-40 weeks), children (2 months-7 years), and adults were immunostained with monoclonal antibodies. The function of the address ins and their lymphocyte counter-receptors was tested in in vitro binding a ssays on fetal and adult tissues. Results: Unlike in adults, MAdCAM-1 is wi dely expressed from embryonic week 7 onwards, and it only gradually becomes polarized to mucosal vessels after birth. In utero MAdCAM-1 functionally g overns lymphocyte adhesion to vessels both in the gut and PLNs by binding t o alpha (4)beta (7) integrin. The later induction of PNAd gradually starts to dominate the binding of lymphocytes to PLNs during childhood. Conclusion s: There are striking age-dependent switches and species-specific variation in the molecular mechanisms of lymphocyte migration. In utero and during e arly childhood, the mucosal addressin MAdCAM-1 plays a dominant role in lym phocyte-endothelial cell adhesion at mucosal and nonmucosal sites.