Suppression of autoimmune arthritis in interleukin‐1‐deficient mice in which T cell activation is impaired due to low levels of CD40 ligand and OX40 expression on T cells

Saijo, Shinobu; Asano, Masahide; Horai, Reiko; Yamamoto, Hiroaki; Iwakura, Yoichiro

doi:10.1002/art.10172

Cited by 78 publications

(50 citation statements)

References 40 publications

(40 reference statements)

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“…Alternatively, these cytokines could potentially compete for IL-1RAcP and its associated signaling components. Soluble ST2 has been shown to attenuate disease severity in collagen-induced arthritis, a model of autoimmune inflammation that is dependent on IL-1 (11,12). In light of our findings, the mechanism for this effect may involve the inhibition of IL-1 signaling via the interaction of soluble ST2 and IL-33 with IL-1RAcP.…”

Section: Discussionsupporting

confidence: 53%

IL-1 Receptor Accessory Protein and ST2 Comprise the IL-33 Receptor Complex

Chackerian¹,

Oldham²,

Murphy³

et al. 2007

The Journal of Immunology

466

369

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IL-33 (IL-1F11) is a recently described member of the IL-1 family of cytokines that stimulates the generation of cells, cytokines, and Igs characteristic of a type 2 immune response. IL-33 mediates signal transduction through ST2, a receptor expressed on Th2 and mast cells. In this study, we demonstrate that IL-33 and ST2 form a complex with IL-1R accessory protein (IL-1RAcP), a signaling receptor subunit that is also a member of the IL-1R complex. Additionally, IL-1RAcP is required for IL-33-induced in vivo effects, and IL-33-mediated signal transduction can be inhibited by dominant-negative IL-1RAcP. The implications of this shared usage of IL-1RAcP by IL-1(α and β) and IL-33 are discussed.

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Section: Discussionsupporting

confidence: 53%

IL-1 Receptor Accessory Protein and ST2 Comprise the IL-33 Receptor Complex

Chackerian¹,

Oldham²,

Murphy³

et al. 2007

The Journal of Immunology

466

369

View full text Add to dashboard Cite

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“…In contrast, IL-1Ra gene transfer in mice inhibited both mitogen-and antigen-induced lymphocyte proliferation, whereas sIL-1RAcP gene transfer has no effect on this parameter. It is known that IL-1 plays an important role in the activation of T lymphocytes in CIA (42). Furthermore, the proliferative activity of T cells is enhanced in IL-1Ra Ϫ/Ϫ mice while decreased in IL-1␣/ ␤ Ϫ/Ϫ mice, highlighting the importance of IL-1 in T cell activation and proliferation (43,44).…”

Section: Discussionmentioning

confidence: 96%

Soluble interleukin‐1 receptor accessory protein ameliorates collagen‐induced arthritis by a different mode of action from that of interleukin‐1 receptor antagonist

Smeets¹,

Joosten²,

Arntz³

et al. 2005

Arthritis & Rheumatism

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Objective. To discern the mode of interleukin-1 (IL-1) inhibition of soluble IL-1 receptor accessory protein (sIL-1RAcP) by comparison with IL-1 receptor antagonist (IL-1Ra) in arthritis.Methods. Adenoviral vectors encoding either sIL1RAcP or IL-1Ra were administered systemically before onset of collagen-induced arthritis in DBA/1 mice. Antibovine type II collagen IgG and IL-6 were quantified in serum. Proliferative response of splenic T cells was determined in the presence of sIL-1RAcP or IL-1Ra. The effect on IL-1 inhibition of recombinant sIL-1RAcP and IL-1Ra was further examined in vitro, using NF-B luciferase reporter cell lines. Quantitative polymerase chain reaction was used to determine the relative messenger RNA expression of the IL-1 receptors.Results. Adenoviral overexpression of both sIL1RAcP and IL-1Ra resulted in amelioration of the collagen-induced arthritis. Both IL-1 antagonists reduced the circulating levels of antigen-specific IgG2a antibodies, but only IL-1Ra was able to inhibit lymphocyte proliferation. By using purified lymphocyte populations derived from NF-B reporter mice, we showed that sIL-1RAcP inhibits IL-1-induced NF-B activity in B cells but not T cells, whereas IL-1Ra inhibited IL-1 on both cell types. A study in a panel of NF-B luciferase reporter cells showed that the sIL-1RAcP inhibits IL-1 signaling on cells expressing either low levels of membrane IL-1RAcP or high levels of IL-1RII.Conclusion. We show that the sIL-1RAcP ameliorated experimental arthritis without affecting T cell immunity, in contrast to IL-1Ra. Our results provide data in support of receptor competition by sIL-1RAcP as an explanation for the different mode of IL-1 antagonism in comparison with IL-1Ra.

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“…15). Reduced expression of CD40L has also been associated with suppression of arthritis in IL-1␣␤ Ϫ/Ϫ mice (42). However, effects on autoantibody expression were mixed with those induced by immunization of type II collagen in a powerful adjuvant, CFA, being unaffected while those in the spontaneous human T cell leukemia virus 1-transgenic model were significantly reduced (42).…”

Section: Discussionmentioning

confidence: 99%

Costimulation Requirements of Induced Murine Systemic Autoimmune Disease

Pollard¹,

Arnush²,

Hultman

et al. 2004

The Journal of Immunology

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Costimulation between T cells and APC is required for productive immune responses. A number of receptor/ligand pairs have been shown to mediate costimulation, including CD28/B7 molecules (CD80 and CD86), CD40/CD40 ligand (CD40L, CD154), and LFA-1 (CD18)/ICAM-1 (CD54). T-B cell costimulation also plays a significant role in autoimmune diseases such as systemic lupus erythematosus. Murine HgCl2-induced autoimmunity (mHgIA) is a T cell-dependent systemic autoimmune disease that shares a number of common pathogenic mechanisms with idiopathic lupus. In this report, the significance of costimulation in mHgIA is examined by attempting to induce disease in mice deficient in either CD40L, CD28, or ICAM-1. Unlike absence of ICAM-1, homozygous deficiencies in either CD40L or CD28 significantly reduced the development of mHgIA. CD40L displayed a gene dosage effect as heterozygous mice also showed reduction of autoantibody responses and immunopathology. Markers of T cell activation such as CD44 and CTLA-4 were associated with disease expression in wild-type and ICAM-1-deficient mice but not in CD40L- or CD28-deficient mice. Absence of CTLA-4 expression in CD40L−/− mice suggests that signaling via both CD28 and CD40L is important for T cell activation and subsequent autoimmunity in mHgIA. Attempts to circumvent the absence of CD40L by increasing CD28 signaling via agonistic Ab failed to elicit CTLA-4 expression. These findings indicate that breaking of self-tolerance in mHgIA requires signaling via both the CD28/B7 and CD40/CD40L pathways.

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Suppression of autoimmune arthritis in interleukin‐1‐deficient mice in which T cell activation is impaired due to low levels of CD40 ligand and OX40 expression on T cells

Abstract: Conclusion. These observations suggest that T cell activation by IL-1 is important for the development of autoimmunity and arthritis in these mice.

Cited by 78 publications

References 40 publications

IL-1 Receptor Accessory Protein and ST2 Comprise the IL-33 Receptor Complex

IL-1 Receptor Accessory Protein and ST2 Comprise the IL-33 Receptor Complex

Soluble interleukin‐1 receptor accessory protein ameliorates collagen‐induced arthritis by a different mode of action from that of interleukin‐1 receptor antagonist

Costimulation Requirements of Induced Murine Systemic Autoimmune Disease

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