The Impact of Id2 on Langerhans Cell Development

The first line of defense against pathogens of our body is provided by cells of the immune system that reside in epithelial tissue. Langerhans cells (LC) and CD8a+ conventiona ldendritic cells (cDC) belong to the DC family that are potent antigen-presenting cells that reside in their special environment until activation. For their proper development and function these cells need to anchor to their surrounding tissue. Id2 is known to be essential for the development of LC and CD8a+ cDC. The research described herein assess the role of Id2 in DC development to demonstrate its importance in the differentiation and anchoring of these cells in their niche. Id2 suppresses Zeb2 expression during final steps of LC and CD8a+ cDC differentiation. Id2–/– LC and CD8a+ cDC show high expression of Zeb2 and accordingly reduced levels of adhesion molecules. Consequently, Id2–/– LC do not stable anchor and are lost from the epidermis during the first weeks after birth. In agreement, Zeb2–/– mice contained increased numbers of LC and CD8a+ cDC and reduced numbers of plasmacytoid DC (pDC). Zeb2–/– pDC express strongly elevated levels of Id2, highlighting that Id2 and Zeb2 inhibit each other. Furthermore, E47 induces Zeb2 expression and deletion of E47 in Id2–/– mice partly rescues anchoring of DC. Typical adhesion molecules, such as E-cadherin and EpCAM, were restored in double knock-out mice. Taken together, the data of this work demonstrate that the stable anchorage of tissue resident DC in their niche is governed by Id2 through inhibition of E47-mediated Zeb2 expression