Lymphatic messengers: Non-antigen soluble mediators from diseased tissues to draining lymph nodes

Tissues deliver not only antigens and cells via afferent lymphatics to draining lymph nodes during immune responses but also deliver soluble molecules that reflect the state of the tissue. In autoimmune diseases, these signals from affected tissues can potentially impact the magnitude or other characteristics of autoimmune responses generated in lymph nodes. Here, we highlight recent studies illustrating the nature of these soluble signals relevant to lupus skin and in lymphatic fluid draining the gut in inflammatory bowel disease. We also highlight the role of lymph node stromal cells as recipients of lymph borne signals. Identifying the molecules delivered from the tissues and how exactly they modulate immune function in draining lymph nodes will help us to better understand aberrant immunity in disease.