D6: the ‘crowd controller’ at the immune gateway

The chemokine-scavenging receptor, D6, is reported to regulate resolution of inflammatory responses. However, recent data also point to an unanticipated role for D6 in coordinating innate and adaptive immune responses. Here, we propose that D6 is essential for preventing inflammatory leukocyte association with lymphatic vasculature. In the absence of D6, inappropriate inflammatory leukocyte accumulation around lymphatic endothelium congests the lymphatic system, impairing fluid and cellular flow from inflamed sites to lymph nodes and reducing efficiency of antigen presentation. Thus, the inability of D6-deficient mice to resolve inflammation may be a byproduct of impaired fluid drainage from inflamed sites and thus we provide a model unifying D6 function in innate and adaptive immune responses.