Collagen-induced arthritis in TNF receptor-1-deficient mice: TNF receptor-2 can modulate arthritis in the absence of TNF receptor-1

Citation
Y. Tada et al., Collagen-induced arthritis in TNF receptor-1-deficient mice: TNF receptor-2 can modulate arthritis in the absence of TNF receptor-1, CLIN IMMUNO, 99(3), 2001, pp. 325-333
Citations number
62
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Clinical Immunolgy & Infectious Disease",Immunology
Journal title
CLINICAL IMMUNOLOGY
ISSN journal
1521-6616 → ACNP
Volume
99
Issue
3
Year of publication
2001
Pages
325 - 333
Database
ISI
SICI code
1521-6616(200106)99:3<325:CAITRM>2.0.ZU;2-S
Abstract
TNF is a potent proinflammatory cytokine important for the development of a rthritis in human and animals. We have investigated the roles of TNF recept or-1 (TNFR1) and TNF receptor-2 (TNFR2) in collagen-induced arthritis (CLA) by inducing CIA in mice genetically deficient in TNFR1. TNFR1(-/-) mice de veloped arthritis with similar incidence and severity as TNFR+/- littermate s, indicating that TNFR1 is redundant for the development of CIA. Anti-type II collagen (CII) antibody levels and T cell responses to CII did not diff er between TNFR1(-/-) mice and controls. Neutralization of TNF with soluble TNF binding protein suppressed the development of arthritis in TNFR1(+/-) mice but not in TNFR1(-/-) mice, indicating that TNFR2 cannot substitute fo r TNFR1 for the proinflammatory function. To further investigate the functi ons of TNFR2, TNFR1-/- mice were injected with murine TNF-cy at different s tages during the course of CIA. Repeated TNF-alpha injection during the ear ly induction phase enhanced the development of arthritis, but inhibited art hritis when administered during the late progression phase. These results s how that the engagement of TNFR2 by TNF is involved in the development of C IA in the absence of TNFR1 and that opposing signals can be transduced by T NFR2. (C) 2001 Academic Press.