Administration of agonistic anti-4-1BB monoclonal antibody leads to the amelioration of inflammatory bowel disease

Lee, Jienny; Lee, Eun Na; Kim, Eun Young; Park, Hae Jung; Chang, Chi Young; Jung, Duk Young; Choi, Sang Hyoun; Lee, Suk Koo; Lee, Kwang‐Woong; Kwon, Ghee Young; Joh, Jae‐Won; Kim, Sung Joo

doi:10.1016/j.imlet.2005.06.001

Cited by 55 publications

(41 citation statements)

References 27 publications

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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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“…Whereas this study showed no significant decrease in the TNF-α levels by MSCs, Lee et al. (29,30) showed that DSG and anti-4-1 BB mAb leads to a decrease in TNF-α levels. However, TNF-α significantly increased only on day 3 but not on day 10 in this study, which can be interpreted as MSCs working more effectively in the later part of the inflammation process and not in the earlier part.…”

Section: Discussioncontrasting

confidence: 75%

Immunomodulatory Effects of Mesenchymal Stem Cells in a Murine Model of TNBS-Induced Colitis

et al. 2010

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“…In contrast, the same agonistic 4-1BB antibody has been found to ameliorate many autoimmune and inflammatory diseases. Anti-4-1BB was shown to enhance the number of CD4+CD25+Foxp3+ Treg in NOD mice [48] and in mice undergoing colitis [49], both situations in which the antibody suppressed these diseases, correlating with a potential proliferation/survival activity on nTreg discussed before. However, it is likely that regulatory activity brought about by stimulating 4-1BB might not always be controlled by these mechanisms, and in some cases it has been suggested to be due to the development of novel regulatory CD8+ T cell populations that do not express Foxp3.…”

Section: Cd8+ Treg and Novel Immune Regulation From 4-1bbmentioning

confidence: 88%

Immune regulation and control of regulatory T cells by OX40 and 4-1BB

Lee

Croft

2008

Cytokine & Growth Factor Reviews

119

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The TNFR family members OX40 (CD134) and 4-1BB (CD137) have been found to play major roles as costimulatory receptors for both CD4 and CD8 T cells. In particular, in many situations, they can control proliferation, survival, and cytokine production, and hence are thought to dictate accumulation of protective T cells during anti-viral and anti-tumor responses and pathogenic T cells during autoimmune reactions. As opposed to simply controlling the activity of naïve, effector, and memory T cells, recent data have suggested that both molecules are also instrumental in controlling the generation and activity of so-called regulatory or suppressor T cells (Treg), perhaps in both positive and negative manners. Part of the action on Treg might function to further promote protective or pathogenic T cells, but alternate activities of OX40 and 4-1BB on Treg are also being described that suggest there might be control by these molecules at multiple levels that will alter the biological outcome when these receptors are ligated. This review specifically focuses on recent studies of regulatory T cells, and regulatory or suppressive activity, that are modulated by OX40 or 4-1BB.

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Administration of agonistic anti-4-1BB monoclonal antibody leads to the amelioration of inflammatory bowel disease

Cited by 55 publications

References 27 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

Immunomodulatory Effects of Mesenchymal Stem Cells in a Murine Model of TNBS-Induced Colitis

Immune regulation and control of regulatory T cells by OX40 and 4-1BB

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