Essential role of TNF receptor superfamily 25 (TNFRSF25) in the development of allergic lung inflammation

Lei Fang, Becky Adkins, Vadim Deyev, Eckhard R. Podack

Research output: Contribution to journalArticle

127 Scopus citations

Abstract

We identify the tumor necrosis factor receptor superfamily 25 (TNFRSF25)/TNFSF15 pair as critical trigger for allergic lung inflammation, which is a cardinal feature of asthma. TNFRSF25 (TNFR25) signals are required to exert T helper cell 2 (Th2) effector function in Th2-polarized CD4 cells and co-stimulate interleukin (IL)-13 production by glycosphingolipid-activated NKT cells. In vivo, antibody blockade of TNFSF15 (TL1A), which is the ligand for TNFR25, inhibits lung inflammation and production of Th2 cytokines such as IL-13, even when administered days after airway antigen exposure. Similarly, blockade of TNFR25 by a dominant-negative (DN) transgene, DN TNFR25, confers resistance to lung inflammation in mice. Allergic lung inflammation - resistant, NKT-deficient mice become susceptible upon adoptive transfer of wild-type NKT cells, but not after transfer of DN TNFR25 transgenic NKT cells. The TNFR25/TL1A pair appears to provide an early signal for Th2 cytokine production in the lung, and therefore may be a drug target in attempts to attenuate lung inflammation in asthmatics.

Original languageEnglish (US)
Pages (from-to)1037-1048
Number of pages12
JournalJournal of Experimental Medicine
Volume205
Issue number5
DOIs
StatePublished - May 12 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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