IL-23 and dendritic cells: What are the roles of their mutual attachment in immune response and immunotherapy?

Li, Yanchun; Yu, Xiuhua; Ma, Yucong; Hua, Shucheng

doi:10.1016/j.cyto.2019.02.018

Cited by 21 publications

(20 citation statements)

References 86 publications

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“…2f, h). IL-23 production in dendritic cells (DCs) is critical in regulating IL-22 production in ILCs 36 . However, butyrate did not affect IL-23p19 expression in LP DCs (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity

et al. 2020

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Innate lymphoid cells (ILCs) and CD4+ T cells produce IL-22, which is critical for intestinal immunity. The microbiota is central to IL-22 production in the intestines; however, the factors that regulate IL-22 production by CD4+ T cells and ILCs are not clear. Here, we show that microbiota-derived short-chain fatty acids (SCFAs) promote IL-22 production by CD4+ T cells and ILCs through G-protein receptor 41 (GPR41) and inhibiting histone deacetylase (HDAC). SCFAs upregulate IL-22 production by promoting aryl hydrocarbon receptor (AhR) and hypoxia-inducible factor 1α (HIF1α) expression, which are differentially regulated by mTOR and Stat3. HIF1α binds directly to the Il22 promoter, and SCFAs increase HIF1α binding to the Il22 promoter through histone modification. SCFA supplementation enhances IL-22 production, which protects intestines from inflammation. SCFAs promote human CD4+ T cell IL-22 production. These findings establish the roles of SCFAs in inducing IL-22 production in CD4+ T cells and ILCs to maintain intestinal homeostasis.

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Section: Resultsmentioning

confidence: 99%

Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity

et al. 2020

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“…Cytokines secreted by these antigenpresenting cells function in the differentiation of naïve T cells, which can pass through the blood vessel wall to reach inflamed tissues [26]. CCR5 plays an important role in the migration of and cytokine secretion from antigenpresenting cells [27,28]. Decreased airway hyperresponsiveness and reduced inflammatory cell infiltration can be observed in CCR5 -/mice [29].…”

Section: Discussionmentioning

confidence: 99%

Antagonistic Peptides That Specifically Bind to the First and Second Extracellular Loops of CCR5 and Anti-IL-23p19 Antibody Reduce Airway Inflammation by Suppressing the IL-23/Th17 Signaling Pathway

Zhang

Liang

Xie

et al. 2020

Mediators of Inflammation

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Asthma is a heterogeneous chronic inflammatory disorder of the airways with a complex etiology, which involves a variety of cells and cellular components. Therefore, the aim of the study was to investigate the effects and mechanisms of antagonistic peptides that specifically bind to the first and second extracellular loops of CCR5 (GH and HY peptides, respectively) and anti-interleukin-23 subunit p19 (anti-IL-23p19) in the airway and thereby mediate inflammation and the IL-23/T helper 17 (Th17) cell pathway in asthmatic mice. An experimental asthma model using BALB/c mice was induced by ovalbumin (OVA) and treated with peptides that are antagonistic to CCR5 or with anti-IL-23p19. The extents of the asthmatic inflammation and mucus production were assessed. In addition, bronchoalveolar lavage fluid (BALF) was collected, the cells were counted, and the IL-4 level was detected by ELISA. The IL-23/Th17 pathway-related protein and mRNA levels in the lung tissues were measured, and the positive production rates of Th17 cells in the thymus, spleen, and peripheral blood were detected. The groups treated with one of the two peptides and/or anti-IL-23p19 showed significant reductions in allergic inflammation and mucus secretion; decreased expression levels of IL-23p19, IL-23R, IL-17A and lactoferrin (LTF); and reduced proportions of Th17 cells in the thymus, spleen, and peripheral blood. Specifically, among the four treatment groups, the anti-IL-23p19 with HY peptide group exhibited the lowest positive production rate of Th17 cells. Our data also showed a significant and positive correlation between CCR5 and IL-23p19 protein expression. These findings suggest that the administration of peptides antagonistic to CCR5 and/or anti-IL-23p19 can reduce airway inflammation in asthmatic mice, most likely through inhibition of the IL-23/Th17 signaling pathway, and the HY peptide can alleviate inflammation not only through the IL-23/Th17 pathway but also through other mechanisms that result in the regulation of inflammation.

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“…The expression of IL23A, the subunit p19 of the type 3 cytokine IL23, was markedly higher in WT than ∆∆stx infected colons. IL23 drives the immune response towards type 3 immunity, which is often activated in response to extracellular pathogens (54), and is generally thought to be produced by dendritic cells (83). Unexpectedly, nearly all of the IL23A signal was detected in colonic epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

Shiga toxin remodels the intestinal epithelial transcriptional response to Enterohemorrhagic Escherichia coli

Warr

Kuehl

Waldor

2020

Preprint

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Enterohemorrhagic Escherichia coli (EHEC) is a food-borne pathogen that causes diarrheal disease and the potentially lethal hemolytic uremic syndrome. We used an infant rabbit model of EHEC infection that recapitulates many aspects of human intestinal disease to comprehensively assess colonic transcriptional responses to this pathogen. Cellular compartment-specific RNA-sequencing of intestinal tissue from animals infected with EHEC strains containing or lacking Shiga toxins (Stx) revealed that EHEC infection elicits a robust response that is dramatically shaped by Stx, particularly in epithelial cells. Many of the differences in the transcriptional responses elicited by these strains were in genes involved in immune signaling pathways, such as IL23A, and coagulation, including F3, the gene encoding Tissue Factor. RNA FISH confirmed that these elevated transcripts were found almost exclusively in epithelial cells. Collectively, these findings suggest that within the intestine, Stx primarily targets epithelial cells, and that the potent Stx-mediated modulation of innate immune signaling skews the host response to EHEC towards type 3 immunity.

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IL-23 and dendritic cells: What are the roles of their mutual attachment in immune response and immunotherapy?

Cited by 21 publications

References 86 publications

Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity

Intestinal microbiota-derived short-chain fatty acids regulation of immune cell IL-22 production and gut immunity

Antagonistic Peptides That Specifically Bind to the First and Second Extracellular Loops of CCR5 and Anti-IL-23p19 Antibody Reduce Airway Inflammation by Suppressing the IL-23/Th17 Signaling Pathway

Shiga toxin remodels the intestinal epithelial transcriptional response to Enterohemorrhagic Escherichia coli

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