Role of regulatory T cell in the pathogenesis of inflammatory bowel disease

Yamada, Akiko; Arakaki, Rieko; Saitō, Masako; Takemoto, Tsunematsu; Kudo, Yasusei; Ishimaru, Naozumi

doi:10.3748/wjg.v22.i7.2195

Cited by 150 publications

(125 citation statements)

References 127 publications

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“…These results are consistent with recent reports from human studies demonstrating decreased levels of Tregs within the lamina propria of the intestine of premature infants afflicted with NEC (23). Interestingly, the balance between these two opposing cell populations has been shown to be of critical relevance in the development of autoimmunity (27) and inflammatory bowel disease (28) further demonstrating the relevance of these cell populations in health and disease. Strikingly, this imbalance can be modulated by enteral administration of the vitamin A metabolite, retinoic acid (Fig.…”

Section: Discussionmentioning

confidence: 99%

Retinoic Acid Improves Incidence and Severity of Necrotizing Enterocolitis by Lymphocyte Balance Restitution and Repopulation of LGR5+ Intestinal Stem Cells

Niño¹,

Sodhi²,

Egan³

et al. 2017

Shock

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Necrotizing enterocolitis (NEC) is the most devastating gastrointestinal disease of the premature infant. We have recently shown that NEC development occurs after an increase in proinflammatory CD4+Th17 (Th17) cells and reduced anti-inflammatory Foxp3+ regulatory T cells (Tregs) to the premature small intestine of mice and humans, which can be experimentally reversed in mice by administration of all-trans retinoic acid (ATRA). We have also shown that NEC is characterized by apoptosis of Lgr5-positive intestinal stem cells (ISCs–Lgr5+cells) within the crypts of Lieberkühn, which are subsequently essential for intestinal homeostasis. We now hypothesize that the normal lymphocyte balance within the lamina propria of the intestine can be achieved via administration of ATRA which restores mucosal integrity by preventing the loss of intestinal stem cells. Utilizing both in vivo and in vitro strategies we now demonstrate that Th17 recruitment and Treg depletion lead to increased apoptosis within ISC niches, significantly impairing proliferative capacity and mucosal healing. ATRA exerted its protective effects by preventing T cell imbalance, ultimately leading to the protection of the ISC pool preventing the development of NEC in mice. These findings raise the exciting possibility that dietary manipulations could prevent and treat NEC by modulating lymphocyte balance and the ISC pool within the newborn small intestine.

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Section: Discussionmentioning

confidence: 99%

Retinoic Acid Improves Incidence and Severity of Necrotizing Enterocolitis by Lymphocyte Balance Restitution and Repopulation of LGR5+ Intestinal Stem Cells

Niño¹,

Sodhi²,

Egan³

et al. 2017

Shock

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“…Other studies have shown that immune cells play a role in controlling inflammation in the colon [24]. Among these immune cells, Tregs have been described as having important roles in regulating the pathogenesis of IBD [25,26], and the balance between Tregs and other T cells in the intestinal tract is known to influence IBD pathogenesis [27].…”

Section: Previous Studies Have Shown That Stem Cells Affect Recipientmentioning

confidence: 99%

TSG-6 in extracellular vesicles from canine mesenchymal stem/stromal is a major factor in relieving DSS-induced colitis

Song

et al. 2019

Preprint

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Mesenchymal stem/stromal cell (MSC)-derived extracellular vesicles (EV) have been reported to be beneficial against dextran sulfate sodium (DSS)-induced colitis in mice. However, the underlying mechanisms have not been fully elucidated. We hypothesize that the tumor necrosis factor-α-stimulated gene/protein 6 (TSG-6) in EVs is a key factor influencing the alleviation of colitis symptoms. DSS-induced colitis mice (C57BL/6, male, n = 6-8/group) were intraperitoneally administered EVs (100 ug/mice) on day 1, 3, and 5; colon tissues were collected on day 10 for histopathological, qRT-PCR, western blot, and immunofluorescence analyses. In mice injected with EV, inflammation was alleviated. Indeed, EVs regulated the levels of pro-and anti-inflammatory cytokines, such as TNF-α, IL-1β, IFN-γ, IL-6, and IL-10 in inflamed colons. However, when injected with TSG-6 depleted EV, the degree of inflammatory relief was reduced. Furthermore, TSG-6 in EVs plays a key role in increasing regulatory T cells (Tregs) in the colon. In conclusion, this study shows that TSG-6 in EVs is a major factor in the relief of DSS-induced colitis, by increasing the number of Tregs in the colon.

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“…For example, in the gut, where constant pathogen interaction occurs, Tregs prevent development of colitis. The loss of this anti-inflammatory mechanism has been shown to play a significant role in inflammatory bowel disease (IBD) [110]. Sun et al found that DCs in the lamina propria of the small intestine drive the maturation of Tregs from CD4+ T helper cells [111].…”

Section: Mechanisms Of Hif-1α Stabilization Activation and Degradatmentioning

confidence: 99%

Hypoxia-inducible factor-1α regulation of myeloid cells

et al. 2018

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Hematopoietic myeloblasts give rise to macrophages, dendritic cells, and neutrophils. Circulating myeloid cells detect invading microbes using pattern recognition receptors and subsequently orchestrate an innate immune response to contain and kill the pathogens. This innate immune response establishes an inflammatory niche characterized by hypoxia due to host and pathogen factors. Hypoxia-inducible factor (HIF) transcription factors are the primary regulators of the myeloid response to hypoxia. In particular, HIF-1α is a critical hub that integrates hypoxic and immunogenic signals during infection or inflammation. Hypoxia induces HIF-1α stabilization, which drives metabolic and phenotypic reprogramming of myeloid cells to maximize antimicrobial potential. HIF-1α activity in myeloid-derived cells enhances the host response to infection but may also play a role in pathogenic inflammatory processes such as atherosclerosis. In this review, we summarize recent advances that have elucidated the mechanism by which myeloid cells regulate HIF-1α activity and, in turn, how HIF-1α shapes myeloid cell function.

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Role of regulatory T cell in the pathogenesis of inflammatory bowel disease

Cited by 150 publications

References 127 publications

Retinoic Acid Improves Incidence and Severity of Necrotizing Enterocolitis by Lymphocyte Balance Restitution and Repopulation of LGR5+ Intestinal Stem Cells

Retinoic Acid Improves Incidence and Severity of Necrotizing Enterocolitis by Lymphocyte Balance Restitution and Repopulation of LGR5+ Intestinal Stem Cells

TSG-6 in extracellular vesicles from canine mesenchymal stem/stromal is a major factor in relieving DSS-induced colitis

Hypoxia-inducible factor-1α regulation of myeloid cells

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