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

Lei Fang, Rebecca D Adkins, Vadim Deyev, Eckhard R. Podack

Research output: Contribution to journalArticle

124 Citations (Scopus)

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

Fingerprint

Tumor Necrosis Factor Receptors
Th2 Cells
Pneumonia
Natural Killer T-Cells
Interleukin-13
Cytokines
Glycosphingolipids
Adoptive Transfer
Transgenes
Asthma
Ligands
Antigens
Lung
Antibodies
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Immunology

Cite this

Essential role of TNF receptor superfamily 25 (TNFRSF25) in the development of allergic lung inflammation. / Fang, Lei; Adkins, Rebecca D; Deyev, Vadim; Podack, Eckhard R.

In: Journal of Experimental Medicine, Vol. 205, No. 5, 12.05.2008, p. 1037-1048.

Research output: Contribution to journalArticle

Fang, Lei ; Adkins, Rebecca D ; Deyev, Vadim ; Podack, Eckhard R. / Essential role of TNF receptor superfamily 25 (TNFRSF25) in the development of allergic lung inflammation. In: Journal of Experimental Medicine. 2008 ; Vol. 205, No. 5. pp. 1037-1048.
@article{08223b69887d4dd2ae8d48ace6cb06e7,
title = "Essential role of TNF receptor superfamily 25 (TNFRSF25) in the development of allergic lung inflammation",
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.",
author = "Lei Fang and Adkins, {Rebecca D} and Vadim Deyev and Podack, {Eckhard R.}",
year = "2008",
month = "5",
day = "12",
doi = "10.1084/jem.20072528",
language = "English",
volume = "205",
pages = "1037--1048",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "5",

}

TY - JOUR

T1 - Essential role of TNF receptor superfamily 25 (TNFRSF25) in the development of allergic lung inflammation

AU - Fang, Lei

AU - Adkins, Rebecca D

AU - Deyev, Vadim

AU - Podack, Eckhard R.

PY - 2008/5/12

Y1 - 2008/5/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=43549110073&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=43549110073&partnerID=8YFLogxK

U2 - 10.1084/jem.20072528

DO - 10.1084/jem.20072528

M3 - Article

C2 - 18411341

AN - SCOPUS:43549110073

VL - 205

SP - 1037

EP - 1048

JO - Journal of Experimental Medicine

JF - Journal of Experimental Medicine

SN - 0022-1007

IS - 5

ER -