Synergy of Transforming Growth Factor Beta 1 and All Trans Retinoic Acid in the Treatment of Inflammatory Bowel Disease: Role of Regulatory T cells

Auci, Dominick L.; Egilmez, Nejat K.

doi:10.15226/2374-815x/3/4/00166

Cited by 7 publications

(5 citation statements)

References 126 publications

(119 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…RA enhances ILC plasticity and induces the production of IL-22 in group 3 ILC cells (ILC3) [25][26][27], which, among other actions, helps regulate the integrity of the intestinal epithelial cells (IEC). Additionally, RA has been shown to attenuate gut inflammation [25,26,[28][29][30] where its local production in the gut is essential for maintaining proper gut homeostasis and innate immune responses [17,[31][32][33]. Mucosal damage in the small intestine induces a local state of vitamin A deficiency (VAD), where limited RA availability inhibits the number and function of cell populations important to gut homeostasis and immune response that rely on the RA signal [4,14,15,23,31,32,34,35].…”

Section: Retinoids In Gut Physiologymentioning

confidence: 99%

Actions of Retinoic Acid in the Pathophysiology of HIV Infection

Sidell

Kane

2022

Nutrients

View full text Add to dashboard Cite

The vitamin A metabolite all-trans retinoic acid (RA) plays a key role in tissue homeostasis and mucosal immunity. RA is produced by gut-associated dendritic cells, which are among the first cells encountered by HIV. Acute HIV infection results in rapid reduction of RA levels and dysregulation of immune cell populations whose identities and function are largely controlled by RA. Here, we discuss the potential link between the roles played by RA in shaping intestinal immune responses and the manifestations and pathogenesis of HIV-associated enteropathy and similar conditions observed in SIV-infected non-human primate models. We also present data demonstrating the ability of RA to enhance the activation of replication-competent viral reservoirs from subjects on suppressive anti-retroviral therapy. The data suggest that retinoid supplementation may be a useful adjuvant for countering the pathologic condition of the gastro-intestinal tract associated with HIV infection and as part of a strategy for reactivating viral reservoirs as a means of depleting latent viral infection.

show abstract

Section: Retinoids In Gut Physiologymentioning

confidence: 99%

Actions of Retinoic Acid in the Pathophysiology of HIV Infection

Sidell

Kane

2022

Nutrients

View full text Add to dashboard Cite

show abstract

“…RA may mitigate IBD severity through various immunoregulatory mechanisms. RA could: (1) restore and/or reprogram the impaired Treg/Th17 lineage differentiation that is usually linked to IBD development [ 51 , 107 ] by inducing adaptive Treg cells and imprinting their gut-homing phenotype in response to inflammatory stimuli [ 108 ]; (2) modulate the recognition of different TLR ligands and control the activation of downstream transcription factor signaling [ 109 , 110 ]; (3) downregulate inflammatory signaling molecules like nitric oxide (NO) from PBMCs of IBD patients, even after the establishment of the pro-inflammatory niche [ 111 ]; (4) regulate the production of immunoregulatory cytokines, such as by enhancing the synthesis of IL-22 by γδ T cells and ILCs and consequently attenuating colitis [ 61 ]; and (5) synergize with immunoregulatory mediators like TGFβ for maintaining gut homeostasis [ 112 ].…”

Section: Efficacies Of Ra In the Treatment Of Autoimmune Diseasesmentioning

confidence: 99%

Retinoic Acid, Leaky Gut, and Autoimmune Diseases

Abdelhamid

Luo

2018

Nutrients

View full text Add to dashboard Cite

A leaky gut has been observed in a number of autoimmune diseases including type 1 diabetes, multiple sclerosis, inflammatory bowel disease, and systemic lupus erythematosus. Previous studies from our laboratory have shown that lupus mice also bear a leaky gut and that the intestinal barrier function can be enhanced by gut colonization of probiotics such as Lactobacillus spp. Retinoic acid (RA) can increase the relative abundance of Lactobacillus spp. in the gut. Interestingly, RA has also been shown to strengthen the barrier function of epithelial cells in vitro and in the absence of probiotic bacteria. These reports bring up an interesting question of whether RA exerts protective effects on the intestinal barrier directly or through regulating the microbiota colonization. In this review, we will discuss the roles of RA in immunomodulation, recent literature on the involvement of a leaky gut in different autoimmune diseases, and how RA shapes the outcomes of these diseases.

show abstract

“…Our observations add to a wide body of literature reporting benefit of ATRA in rodent models of colitis, as we have reviewed. 22,48 Observations included work in mouse DSS, 2,4,6-Trinitrobenzenesulfonic acid (TNBS), 13,14 and TNFΔARE mutation models, 49 along with our own previous work in rodent ACT and DSS IBD models. 19 Observations in humans have been more equivocal, even controversial.…”

Section: Discussionmentioning

confidence: 99%

Oral Delivery of Encapsulated All-Trans Retinoic Acid Ameliorates Disease in Rodent Models of Colitis

Nicoletti

Hammer

Furtado

et al. 2021

Inflammatory Bowel Diseases

View full text Add to dashboard Cite

Background All-trans retinoic acid (ATRA) is a biologically active isomer of retinoic acid (RA). Topical ATRA (retin-a, retin-a micro, atralin, renova, and avita) is the active pharmaceutical ingredient for FDA-approved treatments for acne and skin wrinkles. Oral formulations (Vesanoid) treat acute promyelocytic leukemia, but oral dosing can induce severe side effects. Despite benefits in various rodent models of inflammatory bowel disease (IBD), toxicity and controversial clinical observations have diminished enthusiasm for ATRA IBD clinical trials. To circumvent these issues and to use ATRA’s key role in maintaining gut tolerance, we developed a poly(lactic-co-glycolic acid) (PLGA) microsphere (MS) encapsulated ATRA formulation aimed at directing ATRA delivery to immune structures of the gut, limiting systemic exposure. Initially, ATRA MS was developed as a component of a combinatorial product (TreXTAM) that also contained encapsulated transforming growth factor (TGF)-β and ATRA in a 1:2 w/w ratio. Although the combination was optimal, benefit was also observed when ATRA MS was given alone in the CD4+ CD25-T-cell adoptive transfer (ACT) colitis model. Methods We used the ACT and DSS-induced murine models of colitis to expand on the dose-dependent effects of oral ATRA MS when given alone. The DSS model was also used to compare the efficacy of ATRA MS and soluble ATRA, while healthy animals were used to compare the pharmacokinetics of the two drugs. Results In both the ACT and DSS-induced murine models of colitis, ATRA MS was observed to be effective in ameliorating disease. ATRA MS was also observed to be more effective than soluble ATRA in these models and displayed more favorable pharmacokinetics. Conclusions We suggest ATRA MS, as a standalone product, may attenuate IBD and perhaps limit fibrosis, while limiting systemic side effects.

show abstract

Synergy of Transforming Growth Factor Beta 1 and All Trans Retinoic Acid in the Treatment of Inflammatory Bowel Disease: Role of Regulatory T cells

Cited by 7 publications

References 126 publications

Actions of Retinoic Acid in the Pathophysiology of HIV Infection

Actions of Retinoic Acid in the Pathophysiology of HIV Infection

Retinoic Acid, Leaky Gut, and Autoimmune Diseases

Oral Delivery of Encapsulated All-Trans Retinoic Acid Ameliorates Disease in Rodent Models of Colitis

Contact Info

Product

Resources

About