Abstract
A proliferation-inducing ligand (APRIL or TNFSF13) shares receptors with B-cell activation factor of the TNF family (BAFF) on B and T cells. Although much is known about the function of APRIL in B cells, its role in T cells remains unclear. Blocking both BAFF and APRIL suggested that BAFF and/or APRIL contributed to collagen-induced arthritis (CIA); however, the role of APRIL alone in CIA remained unresolved. We show here that, in vitro, our newly generated APRIL-/- mice exhibited increased T-cell proliferation, enhanced Th2 cytokine production under non-polarizing conditions, and augmented IL-13 and IL-17 production under Th2 polarizing conditions. Upon immunization with OVA and aluminum potassium sulfate, APRIL-/- mice responded with an increased antigen-specific IgG1 response. We also show that in APRIL-/- mice, the incidence of CIA was significantly reduced compared with WT mice in parallel with diminished levels of antigen-specific IgG2a autoantibody and IL-17 production. Our data indicate that APRIL plays an important role in the regulation of cytokine production and that APRIL-triggered signals contribute to arthritis. Blockade of APRIL thus may be a valuable adjunct in the treatment of rheumatoid arthritis.
| Original language | English |
|---|---|
| Pages (from-to) | 3450-3458 |
| Number of pages | 9 |
| Journal | European Journal of Immunology |
| Volume | 38 |
| Issue number | 12 |
| DOIs | |
| State | Published - Dec 1 2008 |
| Externally published | Yes |
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Keywords
- Autoimmunity
- Cytokines
- T cells
- TNF
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
Cite this
APRIL (TNFSF13) regulates collagen-induced arthritis, IL-17 production and Th2 response. / Xiao, Yanping; Motomura, Seiichi; Podack, Eckhard R.
In: European Journal of Immunology, Vol. 38, No. 12, 01.12.2008, p. 3450-3458.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - APRIL (TNFSF13) regulates collagen-induced arthritis, IL-17 production and Th2 response
AU - Xiao, Yanping
AU - Motomura, Seiichi
AU - Podack, Eckhard R.
PY - 2008/12/1
Y1 - 2008/12/1
N2 - A proliferation-inducing ligand (APRIL or TNFSF13) shares receptors with B-cell activation factor of the TNF family (BAFF) on B and T cells. Although much is known about the function of APRIL in B cells, its role in T cells remains unclear. Blocking both BAFF and APRIL suggested that BAFF and/or APRIL contributed to collagen-induced arthritis (CIA); however, the role of APRIL alone in CIA remained unresolved. We show here that, in vitro, our newly generated APRIL-/- mice exhibited increased T-cell proliferation, enhanced Th2 cytokine production under non-polarizing conditions, and augmented IL-13 and IL-17 production under Th2 polarizing conditions. Upon immunization with OVA and aluminum potassium sulfate, APRIL-/- mice responded with an increased antigen-specific IgG1 response. We also show that in APRIL-/- mice, the incidence of CIA was significantly reduced compared with WT mice in parallel with diminished levels of antigen-specific IgG2a autoantibody and IL-17 production. Our data indicate that APRIL plays an important role in the regulation of cytokine production and that APRIL-triggered signals contribute to arthritis. Blockade of APRIL thus may be a valuable adjunct in the treatment of rheumatoid arthritis.
AB - A proliferation-inducing ligand (APRIL or TNFSF13) shares receptors with B-cell activation factor of the TNF family (BAFF) on B and T cells. Although much is known about the function of APRIL in B cells, its role in T cells remains unclear. Blocking both BAFF and APRIL suggested that BAFF and/or APRIL contributed to collagen-induced arthritis (CIA); however, the role of APRIL alone in CIA remained unresolved. We show here that, in vitro, our newly generated APRIL-/- mice exhibited increased T-cell proliferation, enhanced Th2 cytokine production under non-polarizing conditions, and augmented IL-13 and IL-17 production under Th2 polarizing conditions. Upon immunization with OVA and aluminum potassium sulfate, APRIL-/- mice responded with an increased antigen-specific IgG1 response. We also show that in APRIL-/- mice, the incidence of CIA was significantly reduced compared with WT mice in parallel with diminished levels of antigen-specific IgG2a autoantibody and IL-17 production. Our data indicate that APRIL plays an important role in the regulation of cytokine production and that APRIL-triggered signals contribute to arthritis. Blockade of APRIL thus may be a valuable adjunct in the treatment of rheumatoid arthritis.
KW - Autoimmunity
KW - Cytokines
KW - T cells
KW - TNF
UR - http://www.scopus.com/inward/record.url?scp=59749105357&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=59749105357&partnerID=8YFLogxK
U2 - 10.1002/eji.200838640
DO - 10.1002/eji.200838640
M3 - Article
C2 - 19016524
AN - SCOPUS:59749105357
VL - 38
SP - 3450
EP - 3458
JO - European Journal of Immunology
JF - European Journal of Immunology
SN - 0014-2980
IS - 12
ER -