6-Formylindolo (3, 2-b) Carbazole (FICZ)–mediated protection of gut barrier is dependent on T cells in a mouse model of alcohol combined with burn injury

Li, Xiaoling; Luck, Marisa E.; Hammer, Adam M.; Cannon, Abigail R.; Choudhry, Mashkoor A.

doi:10.1016/j.bbadis.2020.165901

Cited by 7 publications

(9 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous work has demonstrated that intestinal T cell responses are diminished following acute ethanol intoxication and burn injury (25,36,37). The goal of this study was to demonstrate whether Tregs may play a role in the aberrant effector T cell responses observed following ethanol intoxication and burn injury.…”

Section: Discussionmentioning

confidence: 95%

Ethanol Intoxication and Burn Injury Increases Intestinal Regulatory T Cell Population and Regulatory T Cell Suppressive Capability

Luck

Herrnreiter

et al. 2021

Shock

Self Cite

View full text Add to dashboard Cite

Traumatic injuries, such as burn, are often complicated by ethanol intoxication at the time of injury. This leads to a myriad of complications and post-burn pathologies exacerbated by aberrant immune responses. Recent findings suggest that immune cell dysfunction in the gastrointestinal system is particularly important in deleterious outcomes associated with burn injuries. In particular, intoxication at the time of burn injury leads to compromised intestinal T cell responses, which can diminish intestinal immunity and promote bacterial translocation, allowing for increased secondary infections in the injured host and associated sequelae, such as multiple organ failure and sepsis. Regulatory T cells (Treg) have been identified as important mediators of suppressing effector T cell function. Therefore, the goal of this study was to assess the effects of ethanol intoxication and burn injury on Treg populations in small intestinal immune organs. We also evaluated the suppressive capability of Tregs isolated from injured animals. Male C57BL/6 mice were gavaged with 2.9 g/kg ethanol before receiving a $12.5% total body surface area scald burn. One day after injury, we identified a significant increase in Tregs number in small intestine Peyer's patches ($Â1.5) and lamina propria ($Â2). Tregs-producing cytokine IL-10 were also increased in both tissues. Finally, Tregs isolated from ethanol and burn-injured mice were able to suppress proliferation of effector Tcells to a greater degree than sham vehicle Tregs. This was accompanied by increased levels of IL-10 and decreased levels of pro-proliferative cytokine IL-2 in cultures containing ethanol þ burn Tregs compared with sham Tregs. These findings suggest that Treg populations are increased in intestinal tissues 1 day following ethanol intoxication and burn injury. Tregs isolated from ethanol and burn-injured animals also exhibit a greater suppression of effector T cell proliferation, which may contribute to altered T cell responses following injury.

show abstract

Section: Discussionmentioning

confidence: 95%

Ethanol Intoxication and Burn Injury Increases Intestinal Regulatory T Cell Population and Regulatory T Cell Suppressive Capability

Luck

Herrnreiter

et al. 2021

Shock

Self Cite

View full text Add to dashboard Cite

show abstract

“…Burn group animals were immersed in $85 C water bath for $7 s to induce a full-thickness scald burn injury. Sham injury animals were placed in a 37 C water bath for $7 s (30,31). After burn or sham injury, the animals were dried gently.…”

Section: Murine Model Of Acute Alcohol Intoxication and Burn Injurymentioning

confidence: 99%

“…Intracellular staining for IL-27 was performed using Foxp3 Transcription Factor Staining Buffer Set (eBioscience) according to the manufacturers instructions with PE-conjugated anti-mouse IL-27 (eBioscience). Flow cytometry data were collected with FACSCanto II (BD Biosciences) and analyzed with FlowJo software (Tree Star) (30).…”

Section: Cell Stimulation and Flow Cytometry Of Lymphocytesmentioning

confidence: 99%

See 1 more Smart Citation

IL-27 Promotes Intestinal Barrier Integrity following Ethanol Intoxication and Burn Injury

Luck

Herrnreiter

et al. 2022

ImmunoHorizons

Self Cite

View full text Add to dashboard Cite

Alcohol intoxication combined with burn injury can lead to life-threatening complications, including sepsis, multiple organ failure, and death. After an acute burn, the gastrointestinal system becomes hypoxic because of fluid loss and reduction of intestinal blood flow. This can cause perturbations in the intestinal epithelial barrier, immune function, and the composition of the gut microbiome. Increased gut permeability leads to proinflammatory signaling, contributing to further damage to the intestinal barrier. Recent studies have suggested that IL-27 plays an anti-inflammatory role, which may be beneficial in intestinal barrier repair. Therefore, in this study, we examined the effect of ethanol and burn injury on IL-27 in the small intestine, as well as the potential beneficial role of IL-27 in restoring the intestinal barrier after intoxication and burn. Male C57BL/6 mice were gavaged with 2.9 g/kg ethanol before receiving a $12.5% total body surface area scald burn with or without rIL-27 in resuscitation fluid. Our results demonstrate that IL-27-producing cells are reduced in the small intestine after injury. When IL-27 is supplemented in resuscitation fluid, we were able to restore intestinal barrier integrity and transit, mediated through increased intestinal epithelial cell proliferation, reduced inflammatory cytokines, and increased anti-inflammatory cytokine IL-10. We also observed increased gene expression of tight junction proteins. These findings suggest that IL-27 may be a contributor to maintaining proper intestinal barrier function after injury through multiple mechanisms, including preventing excess inflammation and promoting intestinal epithelial cell proliferation and tight junction integrity.

show abstract

“…Additionally, FICZ has been shown to play an important role in barrier function. In the small intestine, FICZ treatment enhanced T cell release of IL-17 and IL-22 in the small intestine which induced a protective effect of the intestinal barriers of mice after ethanol and burn injury [ 59 ]. It also shows promise as a therapeutic due to its effects on intraepithelial lymphocytes [ 60 ].…”

Section: Introduction To Ahrmentioning

confidence: 99%

Targeting AhR as a Novel Therapeutic Modality against Inflammatory Diseases

Cannon

Nagarkatti

2021

IJMS

View full text Add to dashboard Cite

For decades, activation of Aryl Hydrocarbon Receptor (AhR) was excluded from consideration as a therapeutic approach due to the potential toxic effects of AhR ligands and the induction of the cytochrome P450 enzyme, Cyp1a1, following AhR activation. However, it is now understood that AhR activation not only serves as an environmental sensor that regulates the effects of environmental toxins, but also as a key immunomodulator where ligands induce a variety of cellular and epigenetic mechanisms to attenuate inflammation. Thus, the emergence of further in-depth research into diverse groups of compounds capable of activating this receptor has prompted reconsideration of its use therapeutically. The aim of this review is to summarize the body of research surrounding AhR and its role in regulating inflammation. Specifically, evidence supporting the potential of targeting this receptor to modulate the immune response in inflammatory and autoimmune diseases will be highlighted. Additionally, the opportunities and challenges of developing AhR-based therapies to suppress inflammation will be discussed.

show abstract

6-Formylindolo (3, 2-b) Carbazole (FICZ)–mediated protection of gut barrier is dependent on T cells in a mouse model of alcohol combined with burn injury

Cited by 7 publications

References 36 publications

Ethanol Intoxication and Burn Injury Increases Intestinal Regulatory T Cell Population and Regulatory T Cell Suppressive Capability

Ethanol Intoxication and Burn Injury Increases Intestinal Regulatory T Cell Population and Regulatory T Cell Suppressive Capability

IL-27 Promotes Intestinal Barrier Integrity following Ethanol Intoxication and Burn Injury

Targeting AhR as a Novel Therapeutic Modality against Inflammatory Diseases

Contact Info

Product

Resources

About