Embryonic macrophages function during early life to determine invariant natural killer T cell levels at barrier surfaces

It is increasingly recognized that immune development within mucosal tissues is under the control of environmental factors during early life. However, the cellular mechanisms that underlie such temporally and regionally restrictive governance of these processes are unclear. Here, we uncover an extrathymic pathway of immune development within the colon that is controlled by embryonic but not bone marrow-derived macrophages, which determines the ability of these organs to receive invariant natural killer T (iNKT) cells and allow them to establish local residency. Consequently, early-life perturbations of fetal-derived macrophages result in persistent decreases of mucosal iNKT cells and is associated with later-life susceptibility or resistance to iNKT cell-associated mucosal disorders. These studies uncover a host developmental program orchestrated by ontogenically distinct macrophages that is regulated by microbiota, and they reveal an important postnatal function of macrophages that emerge in fetal life. Invariant natural killer T (iNKT) cells populate barrier surfaces during an early-life window. Blumberg and colleagues demonstrate that such barrier surface iNKT cells develop via an extrathymic pathway dependent on a specialized population of embryo-derived macrophages.

Automated summary

The study uncovers an important mechanism of immune development within the colon controlled by embryo-derived macrophages, which is associated with the decreased number of iNKT cells in infants and later susceptibility or resistance to iNKT cell-associated mucosal disorders. This mechanism is regulated by microbiota and reveals the crucial postnatal function of macrophages emerging in fetal life.