Structure and function of the thymic microenvironment

Organs are more than the sum of their component parts – functional competence requires that these parts not only be present in the appropriate proportions, but also be arranged and function together in specific ways. The thymus is an excellent example of the connection between cellular organization and organ function. Unlike more familiar organs, such as lung or kidney, the thymus is not organized into easily identifiable structures such as tubes and ordered cell layers, but instead is a complex meshwork of microenvironments through which T cell progenitors migrate, receiving signals that instruct them to differentiate, proliferate, or die. Proper thymic organization is essential to the optimal production of a functional T cell repertoire. During aging, the thymus undergoes involution, largely due to degradation of the TEC microenvironmental compartment, which then fails to support optimal thymocyte development resulting in reduced output of naive T cells. This review will summarize the current state of understanding of the composition and organization of thymic microenvironments and the mechanisms that promote their proper development and function.