APRIL (TNFSF13) regulates collagen-induced arthritis, IL-17 production and Th2 response

Yanping Xiao, Seiichi Motomura, Eckhard R. Podack

Research output: Contribution to journalArticle

30 Citations (Scopus)

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 languageEnglish
Pages (from-to)3450-3458
Number of pages9
JournalEuropean Journal of Immunology
Volume38
Issue number12
DOIs
StatePublished - Dec 1 2008
Externally publishedYes

Fingerprint

Experimental Arthritis
Interleukin-17
B-Lymphocytes
T-Lymphocytes
B-Cell Activation Factor Receptor
Cytokines
Antigens
Interleukin-13
Autoantibodies
Arthritis
Immunization
Rheumatoid Arthritis
Immunoglobulin G
Cell Proliferation
Ligands
Incidence
Therapeutics

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 journalArticle

Xiao, Yanping ; Motomura, Seiichi ; Podack, Eckhard R. / APRIL (TNFSF13) regulates collagen-induced arthritis, IL-17 production and Th2 response. In: European Journal of Immunology. 2008 ; Vol. 38, No. 12. pp. 3450-3458.
@article{9a78a6406a8949f19a36de1447aaba13,
title = "APRIL (TNFSF13) regulates collagen-induced arthritis, IL-17 production and Th2 response",
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.",
keywords = "Autoimmunity, Cytokines, T cells, TNF",
author = "Yanping Xiao and Seiichi Motomura and Podack, {Eckhard R.}",
year = "2008",
month = "12",
day = "1",
doi = "10.1002/eji.200838640",
language = "English",
volume = "38",
pages = "3450--3458",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "12",

}

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 -