The expression of OX40 in immunologically mediated diseases of the gastrointestinal tract (celiac disease, Crohn's disease, ulcerative colitis)

Stüber, Eckhard; Büschenfeld, A; Lüttges, Jutta; Freier, A von; Arendt, Thomas; Fölsch, Ulrich R.

doi:10.1046/j.1365-2362.2000.00658.x

Cited by 46 publications

(31 citation statements)

References 22 publications

(12 reference statements)

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“…Furthermore, a strong downregulation by probiotic strains of T h 1 cytokines, such as IL-2, IFN-c and the proinflammatory IL-17, has been reported in other studies using different model systems (Lee et al 2009;Llopis et al 2009;Reiff et al 2009;Schultz et al 2002). Two other genes relevant to IBD that followed this pattern were TNFRSF9 (also referred to as 4-1BB) and TNFRSF4 (Ox-40) (Lee et al 2005;Stuber et al 2000;Totsuka et al 2003). They are members of the tumor necrosis factor receptor (TNFR) family that sustain T cell numbers and responses after initial CD28-dependent T cell activation (Croft 2009).…”

Section: Discussionsupporting

confidence: 55%

Lactobacillus paracasei and Lactobacillus plantarum strains downregulate proinflammatory genes in an ex vivo system of cultured human colonic mucosa

et al. 2012

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Significant health benefits have been demonstrated for certain probiotic strains through intervention studies; however, there is a shortage of experimental evidence relative to the mechanisms of action. Here, noninvasive experimental procedure based on a colon organ culture system has been used that, in contrast to most experimental in vitro models reported, can preserve natural immunohistochemical features of the human mucosa. This system has been used to test whether commensal lactobacilli (Lactobacillus paracasei BL23, Lactobacillus plantarum 299v and L. plantarum 299v (A -)) were able to hinder inflammation-like signals induced by phorbol 12-myristate 13-acetate (PMA)/ionomycin (IO). Whole genome microarrays have been applied to analyze expression differences, from which mRNA markers could be inferred to monitor the effect of putative probiotic strains under such conditions. Regarding the gene expression, PMA/IO treatment induced not only interleukin (IL)-2 and interferon gamma (IFN-c), as expected, but also other relevant genes related to immune response and inflammation, such as IL-17A, chemokine (C-X-C motif) ligand (CXCL) 9 and CXCL11. The ex vivo culturing did not modify the pattern of expression of those genes or others related to inflammation. Interestingly, this study demonstrated that lactobacilli downregulated those genes and triggered a global change of the transcriptional profile that indicated a clear homeostasis restoring effect and a decrease in signals produced by activated T cells.

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Section: Discussionsupporting

confidence: 55%

Lactobacillus paracasei and Lactobacillus plantarum strains downregulate proinflammatory genes in an ex vivo system of cultured human colonic mucosa

et al. 2012

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“…Bansal-Pakala et al (41) recently reported that OX40 crosslinking can provoke Ag-specific proliferation and cytokine production by CD4 ϩ T cells that are anergic in the absence of the OX40 signal, indicating that OX40 signaling can overcome CD4 ϩ T cell tolerance. Consistent with this, the expression of OX40 and/or OX40L has been demonstrated in the tissues of several immune disorders in humans such as graft-vs-host disease (42), proliferative lupus nephritis (43), rheumatoid arthritis (44), human inflammatory bowel disease (IBD) (45,46), and human inflammatory muscle diseases (47), and in thymomas of patients with myasthenia gravis (48). Despite these suggestive observations, a clear link between the OX40-OX40L interaction and the development of these immune disorder-associated diseases remains to be established.…”

Section: Cells That Have Been Described Cd25mentioning

confidence: 60%

Distinct Roles for the OX40-OX40 Ligand Interaction in Regulatory and Nonregulatory T Cells

Takeda¹,

Ine²,

Killeen

et al. 2004

The Journal of Immunology

274

243

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The OX40 (CD134) molecule is induced primarily during T cell activation and, as we show in this study, is also expressed on CD25+CD4+ regulatory T (Treg) cells. A necessary role for OX40 in the development and homeostasis of Treg cells can be inferred from the reduced numbers of the cells present in the spleens of OX40-deficient mice, and their elevated numbers in the spleens of mice that overexpress the OX40 ligand (OX40L). The homeostatic proliferation of Treg cells following transfer into lymphopenic mice was also found to be potentiated by the OX40-OX40L interaction. Suppression of T cell responses by Treg cells was significantly impaired in the absence of OX40, indicating that, in addition to its homeostatic functions, OX40 contributes to efficient Treg-mediated suppression. However, despite this, we found that CD25−CD4+ T cells became insensitive to Treg-mediated suppression when they were exposed to OX40L-expressing cells, or when they were treated with an agonistic OX40-specific mAb. OX40 signaling could also abrogate the disease-preventing activity of Treg cells in an experimental model of inflammatory bowel disease. Thus, although the data reveal important roles for OX40 signaling in Treg cell development, homeostasis, and suppressive activity, they also show that OX40 signals can oppose Treg-mediated suppression when they are delivered directly to Ag-engaged naive T cells.

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“…OX40 has been reported to be expressed on autoreactive or effector T cells in patients with autoimmune diseases (34,36,40) and inflammatory diseases linked to immune disorders (37)(38)(39). The OX40/OX40L system may thus play a potential key role in the immune regulation of various autoimmune diseases.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, OX40 stimulation has been reported to prevent peripheral tolerance of CD4 ϩ T cells (25), suggesting a possible involvement of the OX40/OX40L system in regulating autoimmunity. Indeed, expression of OX40 and/or OX40L has been demonstrated in the tissues of several immune disorders such as experimental allergic encephalitis (24, 26 -28), experimental inflammatory bowel diseases (IBDs) (29,30), graft-vs-host disease (31)(32)(33), human proliferative lupus nephritis (34), rheumatoid arthritis (35,36), human IBD (37,38), human inflammatory muscle diseases (39), and in thymoma of patients with myasthenia gravis (40). In vivo blockade of OX40/ OX40L interaction has been described not only to suppress ongoing experimental allergic encephalitis (28) and graft-vs-host disease (32,41), but also to ameliorate ongoing colitis in murine models of IBD (29,30), asthma (42), and collagen-induced arthritis (35).…”

mentioning

confidence: 99%

Constitutive OX40/OX40 Ligand Interaction Induces Autoimmune-Like Diseases

Murata

Nose

Ndhlovu

et al. 2002

The Journal of Immunology

112

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The interaction between OX40 and OX40 ligand (OX40L) is suggested to provide T cells with an effective costimulatory signals during T cell-APC interaction. To examine the in vivo effect of constitutive OX40/OX40L interaction during immune regulation, we report the establishment of OX40L-transgenic (OX40L-Tg) mice that constitutively express OX40L on T cells. Markedly elevated numbers of effector memory CD4+ T cells, but not CD8+ T cells, were observed in the secondary lymphoid organs of OX40L-Tg mice. Upon immunization with keyhole limpet hemocyanin in the absence of adjuvant, profound T cell proliferative responses and cytokine productions were seen in the OX40L-Tg mice as compared with wild-type mice. Furthermore, in OX40L-Tg mice administrated with superantigen, this constitutive OX40/OX40L interaction on CD4+ T cells completely prevented normal in vivo clonal T cell deletion. Interestingly, OX40L-Tg mice on the C57BL/6 background spontaneously developed interstitial pneumonia and inflammatory bowel disease that was accompanied with a significant production of anti-DNA Ab in the sera. Surprisingly, these diseases were not evident on the OX40L-Tg mice on the BALB/c strain. However, such inflammatory diseases were successfully reproducible in recombination-activating gene (RAG)2-deficient mice upon transfer of OX40L-Tg CD4+ T cells. Blockade of OX40/OX40L interaction in the recipient RAG2-deficient mice completely prevented disease development. The present results orchestrated in this study indicate that OX40/OX40L interaction may be a vital link in our understanding of T cell-mediated organ-specific autoimmunity.

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The expression of OX40 in immunologically mediated diseases of the gastrointestinal tract (celiac disease, Crohn's disease, ulcerative colitis)

Abstract: OX40 is highly expressed in the gastrointestinal tissue of patients with immunologically mediated bowel diseases. Together with previous studies in animal models for these diseases, the present results point to a potential role of OX40 in their pathogenesis.

Cited by 46 publications

References 22 publications

Lactobacillus paracasei and Lactobacillus plantarum strains downregulate proinflammatory genes in an ex vivo system of cultured human colonic mucosa

Lactobacillus paracasei and Lactobacillus plantarum strains downregulate proinflammatory genes in an ex vivo system of cultured human colonic mucosa

Distinct Roles for the OX40-OX40 Ligand Interaction in Regulatory and Nonregulatory T Cells

Constitutive OX40/OX40 Ligand Interaction Induces Autoimmune-Like Diseases

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