LIGHT regulates inflamed draining lymph node hypertrophy

Mingzhao Zhu, Yajun Yang, Yugang Wang, Zhongnan Wang, Yang Xin Fu

Research output: Contribution to journalArticle

24 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)7156-7163
Number of pages8
JournalJournal of Immunology
Volume186
Issue number12
DOIs
StatePublished - Jun 15 2011

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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