Dysregulation of Metabolic Pathways in Circulating Natural Killer Cells Isolated from Inflammatory Bowel Disease Patients

Zaiatz-Bittencourt, Vanessa; Jones, F. G.; Tosetto, Miriam; Doherty, Glen; Ryan, Elizabeth J.

doi:10.1093/ecco-jcc/jjab014

Cited by 20 publications

(15 citation statements)

References 56 publications

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“…One study looking at the Canarypox‐virus vaccine vector ALVAC found this viral‐vector acts as an adjuvant through a mechanism requiring natural killer cells derived IFN‐γ, DC activation and chemokine secretion 63 . We have recently demonstrated that NK cells isolated from the blood of IBD patients produce markedly reduced levels of IFNγ and this suboptimal NK cell response may impact on the ability of patients with IBD to respond to this class of vaccine 64 …”

Section: Novel Vaccines Against Covid‐19mentioning

confidence: 99%

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Review Article: vaccination for patients with inflammatory bowel disease during the COVID‐19 pandemic

Doherty

Fennessy

Stack

et al. 2021

Aliment Pharmacol Ther

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Background: Poor immune responses are frequently observed in patients with inflammatory bowel disease (IBD) receiving established vaccines; risk factors include immunosuppressants and active disease. Aims: To summarise available information regarding immune responses achieved in patients with IBD receiving established vaccines. Using this information, to identify risk factors in the IBD population related to poor vaccine-induced immunity that may be applicable to vaccines against COVID-19. Methods: We undertook a literature review on immunity to currently recommended vaccines for patients with IBD and to COVID-19 vaccines and summarised the relevant literature. Results: Patients with IBD have reduced immune responses following vaccination compared to the general population. Factors including the use of immunomodulators and anti-TNF agents reduce response rates. Patients with IBD should be vaccinated against COVID-19 at the earliest opportunity as recommended by International Advisory Committees, and vaccination should not be deferred because a patient is receiving immune-modifying therapies. Antibody titres to COVID-19 vaccines appear to be reduced in patients receiving anti-TNF therapy, especially in combination with immunomodulators after one vaccination. Therefore, we should optimise any established risk factors that could impact response to vaccination in patients with IBD before vaccination. Conclusions: Ideally, patients with IBD should be vaccinated at the earliest opportunity against COVID-19. Patients should be in remission and, if possible, have their corticosteroid dose minimised before vaccination. Further research is required to determine the impact of different biologics on vaccine response to COVID-19 and the potential for booster vaccines or heterologous prime-boost vaccinations in the IBD population.

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Section: Novel Vaccines Against Covid‐19mentioning

confidence: 99%

“… 63 We have recently demonstrated that NK cells isolated from the blood of IBD patients produce markedly reduced levels of IFNγ and this suboptimal NK cell response may impact on the ability of patients with IBD to respond to this class of vaccine. 64 …”

Section: Novel Vaccines Against Covid‐19mentioning

confidence: 99%

Review Article: vaccination for patients with inflammatory bowel disease during the COVID‐19 pandemic

Doherty

Fennessy

Stack

et al. 2021

Aliment Pharmacol Ther

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“…In the setting of chronic inflammation, NK cell immunosurveillance capacity may be compromised. In a recent study that addressed metabolic and functional profile of blood circulating NK cells in IBD patients, it was demonstrated that these NK cells produce pro-inflammatory cytokines such as IL-17A and TNF-α ex vivo, but they show limited killing capacity and defective mitochondrial activity [ 164 ] ( Table 1 ). It could be hypothesized that such defects in NK cell killing capacity as observed in IBD patients might contribute to decreased immunosurveillance.…”

Section: The Role Of the Immune System In Ibd-associated Cancermentioning

confidence: 99%

“…Limited killing capacity and mitochondrial activity of circulating NK cells from IBD patients [ 164 ].…”

Section: Figurementioning

confidence: 99%

The Role of the Immune System in IBD-Associated Colorectal Cancer: From Pro to Anti-Tumorigenic Mechanisms

Frigerio

Lartey

D’Haens

et al. 2021

IJMS

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Patients with inflammatory bowel disease (IBD) have increased incidence of colorectal cancer (CRC). IBD-associated cancer follows a well-characterized sequence of intestinal epithelial changes, in which genetic mutations and molecular aberrations play a key role. IBD-associated cancer develops against a background of chronic inflammation and pro-inflammatory immune cells, and their products contribute to cancer development and progression. In recent years, the effect of the immunosuppressive microenvironment in cancer development and progression has gained more attention, mainly because of the unprecedented anti-tumor effects of immune checkpoint inhibitors in selected groups of patients. Even though IBD-associated cancer develops in the background of chronic inflammation which is associated with activation of endogenous anti-inflammatory or suppressive mechanisms, the potential role of an immunosuppressive microenvironment in these cancers is largely unknown. In this review, we outline the role of the immune system in promoting cancer development in chronic inflammatory diseases such as IBD, with a specific focus on the anti-inflammatory mechanisms and suppressive immune cells that may play a role in IBD-associated tumorigenesis.

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“…Clinically, circulating NK cells from IBD patients produce large amounts of proinflammatory cytokines and IL-17A, but have less killing capacity [93]. In fact, NK cells play a pivotal role in the antagonistic response to intestinal bacterial infections by producing IFNγ, but this function may be reduced or altered in IBD patients [4,94]. Interestingly, NK cells seem to be involved in the pathogenesis of the development of malignancies including colitis-associated cancers (CAC); autophagy in NK cells inhibits chronic colitis but seems to promote CAC [95,96].…”

Section: Nk Cellsmentioning

confidence: 99%

Biological Analyses-Derived Translational Findings in the T Cell Receptor Alpha Chain Knockout Mouse as an Experimental Model for Ulcerative Colitis

Mizoguchi

Sadanaga

Okada

2021

IJTM

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Inflammatory bowel disease (IBD) is a group of chronic inflammatory disorders that affects many individuals throughout their lives. Ulcerative colitis (UC) and Crohn’s disease (CD) are two major forms of IBD. Until the early 1990s, a murine model of spontaneous chronic colitis was unavailable. As a major breakthrough in the basic research field of IBD, three genetically manipulated murine chronic colitis models, including interleukin (IL)-2 knockout (KO), IL-10 KO, and T cell receptor alpha chain (TCRα) KO models, were established in 1993. Since then, complicated immunobiological mechanisms during the development of UC have been gradually discovered by utilizing a wide variety of murine models of IBD, including the TCRα KO mouse model. In particular, it has been recognized that four major factors, including enteric, environmental, and immunological factors as well as enteric microbiota are highly and mutually involved in the pathogenesis of UC. As a pioneer of the TCRα KO murine model of UC, our group has identified that the interactions between the unique TCRα-β+ T cell population and antigen-presenting cells, including dendritic cells and B cells, play a key role for the development and regulation of UC-like chronic colitis, respectively. Here we have summarized clinically proven pathogenic and regulatory factors which have been identified by this novel TCRα KO murine model of UC in the past nearly three decades.

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Dysregulation of Metabolic Pathways in Circulating Natural Killer Cells Isolated from Inflammatory Bowel Disease Patients

Cited by 20 publications

References 56 publications

Review Article: vaccination for patients with inflammatory bowel disease during the COVID‐19 pandemic

Review Article: vaccination for patients with inflammatory bowel disease during the COVID‐19 pandemic

The Role of the Immune System in IBD-Associated Colorectal Cancer: From Pro to Anti-Tumorigenic Mechanisms

Biological Analyses-Derived Translational Findings in the T Cell Receptor Alpha Chain Knockout Mouse as an Experimental Model for Ulcerative Colitis

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