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 language | English |
|---|---|
| Pages (from-to) | 1037-1048 |
| Number of pages | 12 |
| Journal | Journal of Experimental Medicine |
| Volume | 205 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 12 2008 |
Fingerprint
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 journal › Article
}
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 -