Remodeling of reactive lymph nodes: Dynamics of stromal cells and underlying chemokine signaling

Lymph nodes (LNs) are secondary immune organs dispersed throughout the body. They are primarily composed of lymphocytes, "transient passengers" that are only present for a few hours. During this time, they extensively interact with a meshwork of stromal cells. Although these cells constitute less than 5% of all LN cells, they are integral to LN function: Stromal cells create a three-dimensional network that provides a rigid backbone for the transport of lymph and generates "roads" for lymphocyte migration. Beyond structural support, the LN stroma also produces survival signals for lymphocytes and provides nutrients, soluble factors, antigens, and immune cells collectively required for immune surveillance and the generation of adaptive immune responses. A unique feature of LNs is their ability to considerably and rapidly change size: the volume and cellularity of inflamed LNs can increase up to 20-fold before returning to homeostatic levels. This cycle will be repeated many times during life and is accommodated by stromal cells. The dynamics underlying this dramatic remodeling are subject of this review. We will first introduce the main types of LN stromal cells and explain their known functions. We will then discuss how these cells enable LN growth during immune responses, with a particular focus on underlying cellular mechanisms and molecular cues. Similarly, we will elaborate on stromal dynamics mediating the return to LN homeostasis, a process that is mechanistically much less understood than LN expansion.