Oral-tolerance induction in diet-induced obese mice

Mito, Natsuko; Kaburagi, Tomoko; Yoshino, Haruka; Imai, Atsushi; Sato, Kazuto

doi:10.1016/j.lfs.2006.03.015

Cited by 11 publications

(13 citation statements)

References 46 publications

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“…Studies using DIO mice have defined a number of alterations in leukocyte function [49–54]. There are data to suggest that the reduction in immune function is not associated with obesity, but rather due to the high-fat diet [55–57]. While it is possible that the high-fat diet (and not obesity) was behind the changes in the immune system response to Ad5-TRAIL/CpG therapy in the DIO mice used in our studies, there are two things that would suggest the high-fat diet was not the cause.…”

Section: Discussionmentioning

confidence: 99%

CpG-mediated modulation of MDSC contributes to the efficacy of Ad5-TRAIL therapy against renal cell carcinoma

James

Anderson

Brincks

et al. 2014

Cancer Immunol Immunother

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Tumor progression occurs through the modulation of a number of physiological parameters, including the development of immunosuppressive mechanisms to prevent immune detection and response. Among these immune evasion mechanisms, the mobilization of myeloid-derived suppressor cells (MDSC) is a major contributor to the suppression of antitumor T-cell immunity. Patients with renal cell carcinoma (RCC) show increased MDSC, and methods are being explored clinically to reduce the prevalence of MDSC and/or inhibit their function. In the present study, we investigated the relationship between MDSC and the therapeutic potential of a TRAIL-encoding recombinant adenovirus (Ad5-TRAIL) in combination with CpG-containing oligodeoxynucleotides (Ad5-TRAIL/CpG) in an orthotopic mouse model of RCC. This immunotherapy effectively clears renal (Renca) tumors and enhances survival, despite the presence of a high frequency of MDSC in the spleens and primary tumor-bearing kidneys at the time of treatment. Subsequent analyses revealed that the CpG component of the immunotherapy was responsible for decreasing the frequency of MDSC in Renca-bearing mice; further, treatment with CpG modulated the phenotype and function of MDSC that remained after immunotherapy and correlated with an increased T-cell response. Interestingly, the CpG-dependent alterations in MDSC frequency and function did not occur in tumor-bearing mice complicated with diet-induced obesity. Collectively, these data suggest that in addition to its adjuvant properties, CpG also enhances antitumor responses by altering the number and function of MDSC.

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Section: Discussionmentioning

confidence: 99%

CpG-mediated modulation of MDSC contributes to the efficacy of Ad5-TRAIL therapy against renal cell carcinoma

James

Anderson

Brincks

et al. 2014

Cancer Immunol Immunother

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“…In response to HFD, sera and VAT from DIO mice show increased levels of pro-inflammatory IgG2c antibody, further evidence that class switching of antibody occurs as a direct consequence of obesity 26 . Oral feeding of protein causes obese mice to make IgG2a/c to protein antigens while the same antigens elicit a less inflammatory IgG1 isotype in lean mice 34 .…”

Section: Pathophysiology Of B Cells In Insulin Resistancementioning

confidence: 99%

B lymphocytes as emerging mediators of insulin resistance

Winer

Shen

et al. 2012

Int J Obes Supp

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Obesity is associated with chronic inflammation of various tissues including visceral adipose tissue (VAT), which contributes to insulin resistance. T cells and macrophages infiltrate VAT in obesity and orchestrate this inflammation. Recently, we made the surprising discovery that B cells are important contributors to this process. Thus, some B cells and the antibodies they produce can promote VAT-associated and systemic inflammation, leading to insulin resistance. This report will focus on the properties of these B cells, and how they contribute to insulin resistance through T-cell modulation and production of pathogenic autoantibodies. Understanding the mechanisms by which B cells contribute to insulin resistance should lead to new antibody-based diagnostics and B-cell modulating therapeutics to manage this increasingly prevalent disease.

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“…This issue could be addressed by normalization of vaccine doses in experimental animals. Mice on a HFD make an IgG2a response to protein antigen despite prior oral feeding of the same protein, which in lean mice suppresses this inflammatory isotype in favor of IgG1 (oral tolerance) [59]. Further investigation is needed to determine whether obesity influences susceptibility to food allergies.…”

Section: B Cell Relationships With Adiposementioning

confidence: 99%

Adaptive immunity and adipose tissue biology

Kaminski

Randall

2010

Trends in Immunology

100

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Studies of immunity typically focus on understanding how hematopoietic cells interact within conventional secondary lymphoid tissues. However, immune reactions and their regulation occur in various environments within the body. Adipose tissue is one context that can influence and be influenced by adjacent and embedded lymphocytes. Despite the abundance and wide distribution of such tissue, and despite a growing obesity epidemic, studies of these interactions have been only marginally appreciated in the past. Here, we review advances in understanding of lymphoid structures within adipose tissue, the relationship between adipose tissue and adaptive immune function, and evidence for how this relationship contributes to obesity-associated diseases.

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Oral-tolerance induction in diet-induced obese mice

Cited by 11 publications

References 46 publications

CpG-mediated modulation of MDSC contributes to the efficacy of Ad5-TRAIL therapy against renal cell carcinoma

CpG-mediated modulation of MDSC contributes to the efficacy of Ad5-TRAIL therapy against renal cell carcinoma

B lymphocytes as emerging mediators of insulin resistance

Adaptive immunity and adipose tissue biology

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