The Role of IL-23 in the Pathogenesis and Therapy of Inflammatory Bowel Disease

Korta, Aleksandra; Kula, Julia; Gomułka, Krzysztof

doi:10.3390/ijms241210172

Cited by 22 publications

(9 citation statements)

References 179 publications

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“…Conversely, CD14 - HLA-DR int pDCs have shown to be the most abundant subset in MLNs either expressing CD11c + or not ( 122 ), especially in CD ( 141 ). High expression of CD11c have also been observed in CD103 + DCs ( 13 ) and CD123 – HLA-DR + DCs, which produce more IL-23 in CD patients than in their UC counterparts ( 142 ), demonstrating the importance of CD11c in the pathogenesis of IBD. In this sense, the chromofungin (CHR), a chromogranin-A derived peptide, CHR has demonstrated protective properties against intestinal inflammation by regulating CD11c of DCs ( 143 ).…”

Section: Dcs and Inflammatory Bowel Diseasementioning

confidence: 98%

Dendritic cells: the yin and yang in disease progression

Jiménez-Cortegana,

Palomares,

Alba

et al. 2024

Front. Immunol.

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Dendritic cells (DCs) are antigen presenting cells that link innate and adaptive immunity. DCs have been historically considered as the most effective and potent cell population to capture, process and present antigens to activate naïve T cells and originate favorable immune responses in many diseases, such as cancer. However, in the last decades, it has been observed that DCs not only promote beneficial responses, but also drive the initiation and progression of some pathologies, including inflammatory bowel disease (IBD). In line with those notions, different therapeutic approaches have been tested to enhance or impair the concentration and role of the different DC subsets. The blockade of inhibitory pathways to promote DCs or DC-based vaccines have been successfully assessed in cancer, whereas the targeting of DCs to inhibit their functionality has proved to be favorable in IBD. In this review, we (a) described the general role of DCs, (b) explained the DC subsets and their role in immunogenicity, (c) analyzed the role of DCs in cancer and therapeutic approaches to promote immunogenic DCs and (d) analyzed the role of DCs in IBD and therapeutic approaches to reduced DC-induced inflammation. Therefore, we aimed to highlight the “yin-yang” role of DCs to improve the understand of this type of cells in disease progression.

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Section: Dcs and Inflammatory Bowel Diseasementioning

confidence: 98%

Dendritic cells: the yin and yang in disease progression

Jiménez-Cortegana,

Palomares,

Alba

et al. 2024

Front. Immunol.

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“…Furthermore, other immune cells also contribute to the production of reactive oxygen species (ROS) during metabolic processes, leading to significant tissue damage ( Piechota-Polanczyk and Fichna, 2014 ; Guan, 2019 ). Simultaneously, the imbalance between helper T cells (Th) and regulatory T cells are essential to the progression of IBD ( Uniken et al, 2017 ; Guan, 2019 ; Qiuping et al, 2021 ; Korta et al, 2023 ). The CD is primarily mediated by Th1 cells, while UC inflammation is mainly caused by Th2 cells ( Uniken et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Resveratrol for inflammatory bowel disease in preclinical studies: a systematic review and meta-analysis

Gu,

Lou,

Zhou

et al. 2024

Front. Pharmacol.

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Background: Inflammatory bowel disease (IBD) is a chronic condition that can be managed with treatment, but it is challenging to get IBD cured. Resveratrol, a non-flavonoid polyphenolic organic compound derived from various plants, has a potential effect on IBD. The current research was set out to investigate the therapeutic effects of resveratrol on animal models of IBD.Methods: A comprehensive search of PubMed, Embase, Web of Science, and Chinese databases was performed. The literature search process was completed independently by two people and reviewed by a third person. The risk of bias in the included literature was assessed using the Collaborative Approach to Meta Analysis and Review of Animal Data from Experimental Stroke (CAMARADES) 10-point quality checklist. The meta-analysis utilized Review Manager 5.4 software to evaluate the efficacy of resveratrol, with histopathological index as the primary outcome measure. Subgroup analysis was conducted based on this indicator. Additionally, meta-analyses were carried out on different outcomes reported in the literature, including final disease activity index, final body weight change, colon length, splenic index, and inflammatory factors.Results: After conducting a thorough literature search and selection process, a total of 28 studies were ultimately included in the analysis. It was found that over half of the selected studies had more than five items with low risk of bias in the bias risk assessment. Relevant datas from included literature indicated that the histopathological index of the resveratrol group was significantly lower than that of the control group (WMD = −2.58 [-3.29, −1.87]). Subgroup analysis revealed that higher doses of resveratrol (>80 mg/kg) had a better efficacy (WMD = −3.47 [-4.97, −1.98]). Furthermore, The data summary and quantitative analysis results of SI and colon length also showed that resveratrol was effective in alleviating intestinal mucosal pathological injury of IBD. In terms of biochemical indicators, the summary analysis revealed that resveratrol affected interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α), transforming growth factor-β (TGF-β), interferon-γ (IFN-γ), malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), and prostaglandin E2 (PGE2) significantly. These effects may be attributed to the mechanism of resveratrol in regulating immune response and inhibiting oxidative stress.Conclusion: This review suggests that resveratrol demonstrated a notable therapeutic impact in preclinical models of IBD, particularly at doses exceeding 80 mg/kg. This efficacy is attributed to the protective mechanisms targeting the intestinal mucosa involved in the pathogenesis of IBD through various pathways. As a result, resveratrol holds promising prospects for potential clinical use in the future.

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“…IL-12 plays a pivotal role in guiding T-cell differentiation toward the Th1 interferon-gamma-producing lineage. IL-23 consists of a complex formed by an IL12p40 subunit paired with a distinct IL-23p19 unit through a disulfide bond [ 10 , 11 ]. IL-23 has a major role in the differentiation of Th-17 cells; in particular, when it interacts with its receptor, it activates the inflammatory cascade through a pathway mediated by the Janus kinase (JAK) and the signal transducer and activator of transcription (STAT) [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

“…IL-23 has a major role in the differentiation of Th-17 cells; in particular, when it interacts with its receptor, it activates the inflammatory cascade through a pathway mediated by the Janus kinase (JAK) and the signal transducer and activator of transcription (STAT) [ 12 ]. IL-23 plays a crucial role in the regulation of the gut immune response, and its dysregulation may contribute to the development or exacerbation of inflammatory conditions [ 10 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

The Role of IL-23 Inhibitors in Crohn’s Disease

Fanizza,

D’Amico,

Lusetti

et al. 2023

JCM

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Promoting a Th17 pathogenic response, the interleukin (IL)-23 pathway is crucial in the pathophysiology of inflammatory bowel disease (IBD). With a favorable safety profile, ustekinumab, a monoclonal antibody targeting the shared p40 component of IL-12/23, is currently approved for the treatment of IBD in patients with disease refractory to corticosteroids and biologic drugs. Risankizumab, mirikizumab, and guselkumab are specific IL-23p19 antagonists tested for the treatment of Crohn’s disease (CD). However, only risankizumab currently has been approved for its treatment. Trials with guselkumab and mirikizumab are currently ongoing, with promising preliminary efficacy and safety results. In this review, we provide a summary of the current knowledge about selective IL-23 inhibitors, focusing on their positioning in the therapeutic algorithm of patients with moderate to severe CD.

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The Role of IL-23 in the Pathogenesis and Therapy of Inflammatory Bowel Disease

Cited by 22 publications

References 179 publications

Dendritic cells: the yin and yang in disease progression

Dendritic cells: the yin and yang in disease progression

Resveratrol for inflammatory bowel disease in preclinical studies: a systematic review and meta-analysis

The Role of IL-23 Inhibitors in Crohn’s Disease

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