IL-33 enhances retinoic acid signaling on CD4+ T cells

Gajardo, Tania; Pérez, Francisco; Terraza, Claudia; Campos‐Mora, Mauricio; Noelle, Randolph J.; Pino‐Lagos, Karina

doi:10.1016/j.cyto.2016.06.016

Cited by 6 publications

(5 citation statements)

References 11 publications

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“…The interplay between RA and different mediators, such as transforming growth factor β (TGFβ) [ 50 ], interleukin 2 (IL-2) [ 51 ], and IL-1 family of inflammatory cytokines [ 52 , 53 ], could drive the Treg–Th17 balance. Here, we will discuss the RA-induced regulation of different T-cell subsets, including CD4 + , CD8 + , and γδ T cells, meditated by RAR signaling.…”

Section: Roles Of Ra On Immunitymentioning

confidence: 99%

Retinoic Acid, Leaky Gut, and Autoimmune Diseases

Abdelhamid

Luo

2018

Nutrients

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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.

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Section: Roles Of Ra On Immunitymentioning

confidence: 99%

Retinoic Acid, Leaky Gut, and Autoimmune Diseases

Abdelhamid

Luo

2018

Nutrients

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“…Indeed, the effects of both OP and RA could be traced to the upregulation of Il27, Il33, Jag2, Dll4, Tnfsf4, Irf4, and Irf8 in BM-DCs. IL-27 supports IL-10 production by CD4 + and CD8 + T cells [20], IL-33 promotes RA signalling in CD4 + T cells and stimulates Treg cell responses [21,42], while binding of Notch ligands enhances Foxp3 expression in CD4 + T cells and helps to maintain Treg cells in vitro and in vivo [22]. In particular, the Notch family ligands Jagged 1 and 2 have been related with the promotion of TGF-β signalling and Foxp3 transcription, while concomitant OX40L-OX40 interaction delivers survival signs, allowing Treg cell expansion [23].…”

Section: Discussionmentioning

confidence: 99%

Ovalbumin-Derived Peptides Activate Retinoic Acid Signalling Pathways and Induce Regulatory Responses Through Toll-Like Receptor Interactions

et al. 2020

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This study investigates the potential of a hydrolysate of ovalbumin with pepsin (OP) to preclude Th2-type immunity by the enhancement of tolerogenic dendritic cells (DCs) and regulatory T (Treg) cells. Through Toll-like receptor (TLR) stimulation, OP enhances the retinoic acid pathway on DCs by means of the induction of aldehyde dehydrogenase enzymes and transforming growth factor beta (TGF-β), and it confers upon DC the ability to upregulate interleukin 10 (IL-10) as well as other tolerance-promoting mediators downstream of TRL signalling, such as IL-27, IL-33, Notch ligands, OX40L, and the transcription factors IRF4 and IRF8. OP-conditioned DCs induce the expansion of Foxp3+ and Tr1 cells in co-culture with CD4+ T cells. Furthermore, OP directly conditions CD4+ T cells from naïve mice, without the mediation of DCs, to express aldehyde dehydrogenase (ALDH) enzymes and, in the presence of the Th2 cytokine IL-4 and exogenous TGF-β, it enhances Foxp3 expression. It is noteworthy that, on CD4+ T cells isolated from egg-allergic mice, OP significantly enriches the levels of Foxp3+ and Foxp3+ RORγt+ CD4+ T cells. In conclusion, we show that food peptides may work, analogously to microbial-driven signals, through TLRs, to promote a tolerogenic phenotype on cells of the innate and adaptive immune system, a property that is further enhanced in the context of a Th2 cytokine-rich environment.

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“…IL-27 supports the differentiation of Foxp3 - Tregs and their IL-10 production ( 166 ). IL-33, released by DCs under the influence of the epithelial alarmin IL-33 itself as well as TLR ligands ( 167 ), promotes RA signalling in CD4 + T cells, enhancing TGF-β-mediated differentiation of Tregs and favouring their accumulation and maintenance ( 168 ). This mechanism likely represents a feedback loop by which alarmins limit inflammatory damage at barrier tissues.…”

Section: Tolerogenic Immune Responses To Dietary Antigensmentioning

confidence: 99%

Intestinal factors promoting the development of RORγt+ cells and oral tolerance

López-Fandiño,

Molina,

Lozano-Ojalvo

2023

Front. Immunol.

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The gastrointestinal tract has to harmonize the two seemingly opposite functions of fulfilling nutritional needs and avoiding the entry of pathogens, toxins and agents that can cause physical damage. This balance requires a constant adjustment of absorptive and defending functions by sensing environmental changes or noxious substances and initiating adaptive or protective mechanisms against them through a complex network of receptors integrated with the central nervous system that communicate with cells of the innate and adaptive immune system. Effective homeostatic processes at barrier sites take the responsibility for oral tolerance, which protects from adverse reactions to food that cause allergic diseases. During a very specific time interval in early life, the establishment of a stable microbiota in the large intestine is sufficient to prevent pathological events in adulthood towards a much larger bacterial community and provide tolerance towards diverse food antigens encountered later in life. The beneficial effects of the microbiome are mainly exerted by innate and adaptive cells that express the transcription factor RORγt, in whose generation, mediated by different bacterial metabolites, retinoic acid signalling plays a predominant role. In addition, recent investigations indicate that food antigens also contribute, analogously to microbial-derived signals, to educating innate immune cells and instructing the development and function of RORγt+ cells in the small intestine, complementing and expanding the tolerogenic effect of the microbiome in the colon. This review addresses the mechanisms through which microbiota-produced metabolites and dietary antigens maintain intestinal homeostasis, highlighting the complementarity and redundancy between their functions.

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IL-33 enhances retinoic acid signaling on CD4+ T cells

Cited by 6 publications

References 11 publications

Retinoic Acid, Leaky Gut, and Autoimmune Diseases

Retinoic Acid, Leaky Gut, and Autoimmune Diseases

Ovalbumin-Derived Peptides Activate Retinoic Acid Signalling Pathways and Induce Regulatory Responses Through Toll-Like Receptor Interactions

Intestinal factors promoting the development of RORγt+ cells and oral tolerance

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