Regulation of Interleukin-23 Expression in Health and Disease

Welsby, Iain; Goriely, Stanislas

doi:10.1007/978-94-024-0921-5_8

Cited by 13 publications

(9 citation statements)

References 145 publications

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“…This is because TSLP targets DCs and DCs are known to be a major source of IL-23 under many homeostatic and pathologic conditions. 37 Moreover, TSLP was shown to induce the production of copious amounts of IL23 in primary human DCs. 38 Importantly, the IL-23/IL-17 immune axis has been recognized as a critical element of innate immune defense against different pathogens.…”

Section: Discussionmentioning

confidence: 99%

TSLP Protects Corneas FromPseudomonas aeruginosaInfection by Regulating Dendritic Cells and IL-23-IL-17 Pathway

Cui

Gao

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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PurposeWe sought to determine the role of epithelium-produced thymic stromal lymphopoietin (TSLP) and its underlying mechanisms in corneal innate immune defense against Pseudomonas (P.) aeruginosa keratitis.MethodsThe expression of TSLP and TSLPR in cultured human corneal epithelial cells (HCECs) and mouse corneas was determined by PCR, Western, and/or ELISA. Cellular localization of TSLP receptor (TSLPR) was determined by whole mount confocal microscopy. TSLP-TSLPR signaling was downregulated by neutralizing antibodies and/or small interfering (si)RNA; their effects on the severity of P. aeruginosa–keratitis and cytokine expression were assessed using clinical scoring, bacterial counting, PMN infiltration, and real-time PCR. The role of dendritic cells (DCs) in corneal innate immunity was determined by local DC depletion using CD11c-DTR mice.ResultsP. aeruginosa–infection induced the expression of TSLP and TSLPR in both cultured primary HCECs and in C57BL/6 mouse corneas. While TSLP was mostly expressed by epithelial cells, CD11c-positive cells were positive for TSLPR. Targeting TSLP or TSLPR with neutralizing antibodies or TSLPR with siRNA resulted in more severe keratitis, attributable to an increase in bacterial burden and PMN infiltration. TSLPR neutralization significantly suppressed infection-induced TSLP and interleukin (IL)-17C expression and augmented the expression of IL-23 and IL-17A. Local depletion of DCs markedly increased the severity of keratitis and exhibited no effects on TSLP and IL-23 expression while suppressing IL-17A and C expression in P. aeruginosa–infected corneas.ConclusionsThe epithelium-expressed TSLP plays a protective role in P. aeruginosa keratitis through targeting of DCs and in an IL-23/IL-17 signaling pathway-related manner.

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Section: Discussionmentioning

confidence: 99%

TSLP Protects Corneas FromPseudomonas aeruginosaInfection by Regulating Dendritic Cells and IL-23-IL-17 Pathway

Cui

Gao

et al. 2018

Invest. Ophthalmol. Vis. Sci.

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“…Interestingly, γδT cells showed detectable expression levels of IL-12Rβ1, IL-12Rβ2 and IL-23R [ 92 ]. Antigen-presenting cells (APCs), which are present or recruited to barrier tissues, e.g., gut, skin and lung mainly produce IL-23 [ 93 ]. The cytokine promotes the maturation of pathogenic TH17 cells expressing IL-17, IFN-γ, IL-22 and GM-CSF and resulting in chronic tissue inflammation [ 6 , 94 ].…”

Section: Insights Into Il-12 and Il-23 Signal Transductionmentioning

confidence: 99%

IL-12 and IL-23—Close Relatives with Structural Homologies but Distinct Immunological Functions

Floß

Moll

Scheller

2020

Cells

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Cytokines of the IL-12 family show structural similarities but have distinct functions in the immune system. Prominent members of this cytokine family are the pro-inflammatory cytokines IL-12 and IL-23. These two cytokines share cytokine subunits and receptor chains but have different functions in autoimmune diseases, cancer and infections. Accordingly, structural knowledge about receptor complex formation is essential for the development of new therapeutic strategies preventing and/or inhibiting cytokine:receptor interaction. In addition, intracellular signaling cascades can be targeted to inhibit cytokine-mediated effects. Single nucleotide polymorphisms can lead to alteration in the amino acid sequence and thereby influencing protein functions or protein–protein interactions. To understand the biology of IL-12 and IL-23 and to establish efficient targeting strategies structural knowledge about cytokines and respective receptors is crucial. A highly efficient therapy might be a combination of different drugs targeting extracellular cytokine:receptor assembly and intracellular signaling pathways.

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“…Alteration in the interleukin-23 (IL-23)/Th17 signaling axis has been suggested as an important trigger for chronic inflammation [66,67,68,69,70,71,72]. Briefly, this pathway corresponds to the polarization of naïve CD4 positive cells towards a T-helper cell (Th17) phenotype, associated with by the predominant production of IL-17 and IL-22.…”

Section: How the Gut Microbiome Affects Asmentioning

confidence: 99%

A Possible Role of Intestinal Microbiota in the Pathogenesis of Ankylosing Spondylitis

Yang

Wang

et al. 2016

IJMS

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Ankylosing spondylitis (AS) is a chronic inflammatory disease primarily affecting the sacroiliac joints and the spine, for which the pathogenesis is thought to be a result of the combination of host genetic factors and environmental triggers. However, the precise factors that determine one’s susceptibility to AS remain to be unraveled. With 100 trillion bacteria residing in the mammalian gut having established a symbiotic relation with their host influencing many aspects of host metabolism, physiology, and immunity, a growing body of evidence suggests that intestinal microbiota may play an important role in AS. Several mechanisms have been suggested to explain the potential role of the microbiome in the etiology of AS, such as alterations of intestinal permeability, stimulation of immune responses, and molecular mimicry. In this review, the existing evidence for the involvement of the microbiome in AS pathogenesis was discussed and the potential of intestinal microbiome-targeting strategies in the prevention and treatment of AS was evaluated.

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Regulation of Interleukin-23 Expression in Health and Disease

Cited by 13 publications

References 145 publications

TSLP Protects Corneas FromPseudomonas aeruginosaInfection by Regulating Dendritic Cells and IL-23-IL-17 Pathway

TSLP Protects Corneas FromPseudomonas aeruginosaInfection by Regulating Dendritic Cells and IL-23-IL-17 Pathway

IL-12 and IL-23—Close Relatives with Structural Homologies but Distinct Immunological Functions

A Possible Role of Intestinal Microbiota in the Pathogenesis of Ankylosing Spondylitis

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