Tumor necrosis factor-dependent segmental control of MIG expression by high endothelial venules in inflamed lymph nodes regulates monocyte recruitment

Monocytes recruited from the blood are key contributors to the nature of an immune response. While monocyte recruitment in a subset of immunopathologi es has been well studied and largely attributed to the chemokine monocyte c hemoattractant protein (MCP)-1, mechanisms mediating such recruitment to ot her sites of inflammation remain elusive. Here, we showed that localized in flammation resulted in an increased binding of monocytes to perifollicular high endothelial venules (HEVs) of lymph nodes draining a local inflammator y site. Quantitative PCR analyses revealed the upregulation of many chemoki nes in the inflamed lymph node, including MCP-1 and MIG. HEVs did not expre ss detectable levels of MCP-1; however, a subset of HEVs in inflamed lymph nodes in wild-type (but not tumor necrosis factor [TNF] null mice) expresse d MIG and this subset of HEVs preferentially supported monocyte binding. Ex pression of CXCR3, the receptor for MIG, vas detected on a small subset of peripheral blood monocytes and on a significant percentage of recruited mon ocytes. Most importantly, in both ex vivo and in vivo assays, neutralizing anti-MIG antibodies blocked monocyte binding to inflamed lymph node HEVs. T ogether, these results suggest that the lymph node microenvironment can dic tate the nature of molecules expressed on HEV subsets in a TNF-dependent fa shion and that inflammation-induced MIG expression by HEVs can mediate mono cyte recruitment.