Wnt–β-catenin activation epigenetically reprograms Treg cells in inflammatory bowel disease and dysplastic progression

Quandt, Jasmin; Arnovitz, Stephen; Haghi, Leila; Woehlk, Janine; Mohsin, Azam; Okoreeh, Michael K; Mathur, Priya; Emmanuel, Akinola Olumide; Osman, Abu; Krishnan, Manisha; Morin, Samuel; Pearson, Alexander T.; Sweis, Randy F.; Pekow, Joel; Weber, Christopher; Khazaie, Khashayarsha; Gounari, Fotini

doi:10.1038/s41590-021-00889-2

Cited by 48 publications

(37 citation statements)

References 70 publications

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“…Accumulation of Tregs, particularly eTregs, within the tumor represents a major obstacle to the development of effective anti-tumor immunity (11)(12)(13). The frequency of Tregs among tumor-infiltrating lymphocytes (TIL) is often associated with poor prognosis of patients with many types of cancer (14), although Tregs can also be beneficial during early stages of inflammation-related cancers, such as colorectal cancer, and correlate with better prognosis (15)(16)(17)(18). Substantial reviews have discussed the homeostatic regulation of Tregs and their suppressive function, including the most recent one centering on tumoral Tregs (19).…”

Section: Introductionmentioning

confidence: 99%

Lineage Reprogramming of Effector Regulatory T Cells in Cancer

Dixon

Leavenworth

2021

Front. Immunol.

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Regulatory T-cells (Tregs) are important for maintaining self-tolerance and tissue homeostasis. The functional plasticity of Tregs is a key feature of this lineage, as it allows them to adapt to different microenvironments, adopt transcriptional programs reflective of their environments and tailor their suppressive capacity in a context-dependent fashion. Tregs, particularly effector Tregs (eTregs), are abundant in many types of tumors. However, the functional and transcriptional plasticity of eTregs in tumors remain largely to be explored. Although depletion or inhibition of systemic Tregs can enhance anti-tumor responses, autoimmune sequelae have diminished the enthusiasm for such approaches. A more effective approach should specifically target intratumoral Tregs or subvert local Treg-mediated suppression. This mini-review will discuss the reported mechanisms by which the stability and suppressive function of tumoral Tregs are modulated, with the focus on eTregs and a subset of eTregs, follicular regulatory T (TFR) cells, and how to harness this knowledge for the future development of new effective cancer immunotherapies that selectively target the tumor local response while sparing the systemic side effects.

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Section: Introductionmentioning

confidence: 99%

Lineage Reprogramming of Effector Regulatory T Cells in Cancer

Dixon

Leavenworth

2021

Front. Immunol.

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“…When the components of pathogens (for example LPS) or their pathogen-associated molecular patterns are recognized by the innate immune system, multiple signaling pathways will be initiated to eradicate infection and protect the host against pathogens (Stokes et al, 2015;Iida et al, 2018;Kumar, 2019). Increasing evidence has revealed that the Wnt/β-catenin signaling pathway is involved in several inflammatory diseases (Mu et al, 2020;Quandt et al, 2021;Zhou et al, 2021). Therefore, pharmacological inhibition or interference of the Wnt/β-catenin pathway may be an effective strategy for treatment of several inflammatory diseases.…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Lentinan Against Lipopolysaccharide-Induced Mastitis in Mice

et al. 2021

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Mastitis is a worldwide production disease in dairy cows, which mainly affects milk yield, causing huge economic losses to dairy farmers. Lentinan is a kind of polysaccharide extracted from Lentinus edodes, which has no toxicity and possesses various pharmacological activities including antibacterial and immunomodulatory effects. Therefore, the anti-inflammatory function of lentinan on LPS-stimulated mastitis was carried out, and the mechanism involved was explored. In vivo, lentinan greatly reduced LPS-stimulated pathological injury, myeloperoxidase (MPO) activity, and the proinflammatory factor production (TNF-α and IL-1β) in mice. Further study was performed to determine the activation of the Wnt/β-catenin pathway during LPS stimulation. These results suggested that LPS-induced activation of the Wnt/β-catenin pathway was suppressed by lentinan administration. In vitro, we observed that the mouse mammary epithelial cell (mMEC) viability was not affected by lentinan treatment. As expected, LPS increased the TNF-α and IL-1β protein secretion and the activation of the Wnt/β-catenin pathway that was inhibited by lentinan administration in a dose-dependent manner in mMECs. Conclusively, lentinan exerts the anti-inflammatory function in LPS-stimulated mastitis via inhibiting the activation of the Wnt/β-catenin pathway. Thus, the results of our study also gave an insight that lentinan may serve as a potential treatment for mastitis.

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“…Other cell types involved in cancer-associated inflammation include natural killers, T-helpers, monocytes and regulatory T-cells. During IBD and progression to dysplasia, the regulatory T cells, expressing the Th17-related transcription factor RORγt, increase in the tumor and peripheral blood of individuals with IBD-CRC, releasing pro-inflammatory cytokines (Quandt et al, 2021). Authors linked this phenotype to enhanced Wnt-β-catenin signaling, inducing proinflammatory cytokine production and RORγt expression in Treg cells.…”

Section: Grivennikov Et Al (2009)mentioning

confidence: 99%

Inflammatory Bowel Disease and Risk of Colorectal Cancer: An Overview From Pathophysiology to Pharmacological Prevention

et al. 2021

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Increased risk of colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients has been attributed to long-standing chronic inflammation, with the contribution of genetic alterations and environmental factors such as the microbiota. Moreover, accumulating data indicate that IBD-associated CRC (IBD-CRC) may initiate and develop through a pathway of tumorigenesis distinct from that of sporadic CRC. This mini-review summarizes the current knowledge of IBD-CRC, focusing on the main mechanisms underlying its pathogenesis, and on the important role of immunomodulators and biologics used to treat IBD patients in interfering with the inflammatory process involved in carcinogenesis.

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Wnt–β-catenin activation epigenetically reprograms Treg cells in inflammatory bowel disease and dysplastic progression

Cited by 48 publications

References 70 publications

Lineage Reprogramming of Effector Regulatory T Cells in Cancer

Lineage Reprogramming of Effector Regulatory T Cells in Cancer

Protective Effects of Lentinan Against Lipopolysaccharide-Induced Mastitis in Mice

Inflammatory Bowel Disease and Risk of Colorectal Cancer: An Overview From Pathophysiology to Pharmacological Prevention

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