Immigrant IPCs (red) are found clustered near specialized venules (center) in inflamed lymph nodes.

On page 687, Diacovo and colleagues describe how natural interferon-producing cells (IPCs) make their way from the bloodstream into the peripheral lymph nodes (PLNs), where they help fight pathogens.

IPCs, also called plasmacytoid dendritic cells (DCs), are the major producers of type I interferons and respond to virus infection using intracellular Toll-like receptors that bind viral RNA or DNA. During infection, IPCs accumulate in secondary lymphoid tissue where they boost the antiviral function of other cells, including natural killer cells and DCs, but how they gain entry into the lymph nodes had been a mystery until now.

Using intravital microscopy, which enables real-time viewing of cellular movement in vivo, Diacovo and colleagues showed how inflammation drives IPC migration into PLNs. The important players in this process were adhesion molecules called selectins. L-selectin expressed on the surface of blood-borne IPCs and E-selectin expressed on specialized endothelial venules in the PLNs promoted IPC attachment to and rolling along the vessel endothelium during inflammation. β1- and β2-integrins expressed on the cell surface then allowed IPCs to establish a firm foothold on the vessel wall. Finally, the chemokine receptor CCR5 was shown to be necessary for the IPCs to squeeze through the endothelial cells lining the vessel wall into the PLNs.

These findings distinguish IPC migration patterns from those of conventional DCs, which migrate into the lymph node from peripheral tissues through afferent lymphatics. The authors suggest that IPCs might use the same receptors to gain access to other inflamed tissues such as the skin. If so, interfering with the function of these receptors might be therapeutic in the treatment of autoimmune disorders, such as psoriasis and systemic lupus erythematosus, in which IPCs accumulate in the skin and contribute to disease pathogenesis.