Lymph node (LN) hypertrophy is one of the most basic clinical signs related to acute infection, inflammation, and tumor metastasis; it is thought to be the major indication for initiation and expansion of adaptive immune responses. During LN hypertrophy, dramatic changes in leukocyte trafficking take place. In addition, stromal cell function and number also change significantly accompanying LN hypertrophy, steps that might play pivotal roles in regulating leukocyte trafficking. The cellular and molecular mechanisms of the dynamic LN hypertrophy process, however, are not well defined.

Dr. Mingzhao Zhu, from the Institute of Biophysics, Chinese Academy of Sciences, and Dr. Yang-Xin Fu, from the University of Chicago, have recently revealed that LIGHT (TNFSF14) is a novel factor essential for LN hypertrophy after CFA immunization. Mechanistically, LIGHT is required for the influx of lymphocytes into but not egress out of LNs. In addition, LIGHT is required for dendritic cell migration from the skin to draining LNs. Compared with wild type mice, LIGHT−/− mice express lower levels of chemokines in skin and addressins in LN vascular endothelial cells after CFA immunization. Unexpectedly, LIGHT from radioresistant rather than radiosensitive cells, likely Langerhans cells, is required for LN hypertrophy. Importantly, Ag-specific T cell responses were impaired in draining LNs of LIGHT−/− mice, suggesting the importance of LIGHT regulation of LN hypertrophy in the generation of an adaptive immune response. Collectively, this study reveals a novel cellular and molecular mechanism for the regulation of LN hypertrophy and its potential impact on the generation of an optimal adaptive immune response.

This work was published in the latest issue of the Journal of Immunology (http://www.jimmunol.org/content/186/12/7156.long).

Figure 1: LIGHT regulates dendritic cells and lymphocytes migration to inflammatory lymph node.