title: LIGHT regulates inflamed draining lymph node hypertrophy.
abstract: Lymph node (LN) hypertrophy, the increased cellularity of LNs, is the major indication of the initiation and expansion of the immune response against infection, vaccination, cancer, or autoimmunity. The mechanisms underlying LN hypertrophy remain poorly defined. In this article, we demonstrate that LIGHT (homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for HVEM, a receptor expressed by lymphocytes) (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. We unexpectedly observed that 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, our data reveal 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.
authors.affiliation: Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. zhumz@ibp.ac.cn
authors.forename: Mingzhao
authors.initials: M
authors.lastname: Zhu
authors.forename: Yajun
authors.initials: Y
authors.lastname: Yang
authors.forename: Yugang
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhongnan
authors.initials: Z
authors.lastname: Wang
authors.forename: Yang-Xin
authors.initials: YX
authors.lastname: Fu
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D018925:Chemokines / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D006984:Hypertrophy / Q000473:pathology*; D007114:Immunization; D007249:Inflammation / Q000473:pathology*; D008198:Lymph Nodes / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14 / Q000276:immunology* / Q000502:physiology
chemical_list: D018925:Chemokines; C505915:Tnfsf14 protein, mouse; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14