Dendritic Cell Expression of the Signaling Molecule TRAF6 Is Critical for Gut Microbiota-Dependent Immune Tolerance

Han, Daehee; Walsh, Matthew C.; Cejas, Pedro J.; Dang, Nicholas N.; Kim, Youngmi F.; Kim, Jihyun; Charrier-Hisamuddin, Laetitia; Chau, Lillian; Zhang, Qin; Bittinger, Kyle; Bushman, Frederic D.; Turka, Laurence A.; Shen, Hao; Reizis, Boris; DeFranco, Anthony L.; Wu, Gary D.; Choi, Yongwon

doi:10.1016/j.immuni.2013.05.012

Cited by 68 publications

(60 citation statements)

References 44 publications

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“…Conversely, increased activity of DCs can lead to autoimmunity, often from aberrant cytokine production or inappropriate activation of autoreactive T cells. This was seen when Itgax-cre was used to delete inhibitory signaling molecules such as Fas (Stranges et al, 2007) β-catenin (Manicassamy et al, 2010), FADD (Young et al, 2013), A20 (Hammer et al, 2011), TRAF6 (Han et al, 2013), Lyn (Lamagna et al, 2013), and Caspase-8 (Cuda et al, 2014). …”

Section: Functions Of Dendritic Cellsmentioning

confidence: 99%

Functions of Murine Dendritic Cells

2016

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Dendritic cells (DCs) play critical roles in activating innate immune cells and initiating adaptive immune responses. The functions of DCs were originally obscured by their overlap with other mononuclear phagocytes, but new mouse models have allowed for the selective ablation of subsets of DCs and have helped to identify their non-redundant roles in the immune system. These tools have elucidated the functions of DCs in host defense against pathogens, autoimmunity, and cancer. This review will describe the mouse models generated to interrogate the role of DCs, and will discuss how their use has progressively clarified our understanding of the unique functions of DC subsets.

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Section: Functions Of Dendritic Cellsmentioning

confidence: 99%

Functions of Murine Dendritic Cells

2016

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“…4 The incidence of IBD has been rapidly increasing in many parts of the world, including Asia, typically occurring first in more-industrialized countries. 5 This contributed to the hypothesis that Westernization of our lifestyle is linked to the rising incidence of IBD, as well as other immune-mediated diseases.…”

Section: Epidemiologymentioning

confidence: 99%

Diet in the Pathogenesis and Treatment of Inflammatory Bowel Diseases

et al. 2015

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Some of the most common symptoms of the inflammatory bowel diseases (IBD, which include ulcerative colitis and Crohn’s disease) are abdominal pain, diarrhea, and weight loss. It is therefore not surprising that clinicians and patients have wondered whether dietary patterns influence the onset or course of IBD. The question of what to eat is among the most commonly asked by patients and among the most difficult to answer by clinicians. There are therefore substantial variations in dietary behaviors of patients and recommendations for them, although clinicians do not routinely endorse specific diets for patients with IBD. Dietary clinical trials have been limited by their inability to include a placebo control, contamination of study groups, and inclusion of patients receiving medical therapies. Further challenges include accuracy of information on dietary intake, complex interactions between foods consumed, and differences in food metabolism among individuals. We review the roles of diet in the etiology and management of IBD, based on plausible mechanisms and clinical evidence. Researchers have learned much about the effects of diet on the mucosal immune system, epithelial function, and the intestinal microbiome; these findings could have significant practical implications. Controlled studies of patients receiving enteral nutrition and observations made from patients on exclusion diets have shown that components of whole foods can have deleterious effects for patients with IBD. Additionally, studies in animal models suggested that certain nutrients can reduce intestinal inflammation. In the future, engineered diets that restrict deleterious components but supplement beneficial nutrients could be used to modify the luminal intestinal environment of patients with IBD—these might be used alone or in combination with immunosuppressive agents, or as salvage therapy for patients who do not respond or lose responsiveness to medical therapies. Stricter diets might be required to induce remission, whereas more sustainable exclusion diets could be used to maintain long-term remission.

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“…In particular, it has been shown that DC-derived IL-2 is required for full NK activation (Granucci et al, 2004;, T-cell priming (Granucci et al, 2001;Wuest et al, 2011) and T reg homeostasis (Kulhankova et al, 2012;Sgouroudis et al, 2011;. This last function appears to be particularly relevant for the maintenance of immune tolerance in the gut (Han et al, 2013). By controlling the production of Nur77, a pro-apoptotic factor (Lin et al, 2004), the CD14-dependent transcriptional module regulates the DC-life cycle.…”

Section: The Cd14-dependent Transcriptional Response To Lpsmentioning

confidence: 99%