THE DEVELOPMENT OF SECONDARY LYMPHOID ORGANS

The development of lymph nodes (LN) begins at embryonic day E10.5 with the budding of endothelial cells from veins and the subsequent formation of lymphoid sacs. The lumen of lymphoid sacs contains stromal and endothelial cells that express integrin receptors and chemokines. These signals induce migration into the lymphoid sacs of a specialized population of cells termed LN organizers, because of their central role in LN development. Integrins and chemokine receptors direct LN organizers to lymphoid sacs and induce their activation upon interaction with stromal and endothelial cells. In return, LN organizers, via surface lymphotoxin a ₁b ₂, induce these mesenchymal cells to increase production of chemokines and to upregulate homing receptors for B and T cells, such as ICAM-1 and VCAM-1. Newly produced B and T cells then migrate to nascent LNs and contribute to the formation of a mature LN. We have previously shown that the orphan nuclear hormone receptor RORg is required for the development of LNs, since LNs are absent in RORg -deficient mice. The RORg isoform RORg _t is exclusively expressed in adult thymus and in embryonic LN organizers. In CD4+8+ thymocytes, RORg _t is required for expression of Bcl-xL and for survival of these cells. In the absence of RORg _t, LN organizers fail to develop. In mice expressing EGFP under control of the RORg _t gene, it is now possible to follow maturation and migration of LN organizers, as well as to monitor their role in the cascade of events that leads to the development of a mature LN. On the molecular level, we aim to identify proteins and genes that are modulated by RORg _t during LN development. The study of RORg _t will deepen our understanding of both LN development and regulation of immunity by nuclear hormone receptors.

Selected Publications

   
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