IL-24: A new player in the pathogenesis of pro-inflammatory and allergic skin diseases

Mitamura, Yasutaka; Nunomura, Satoshi; Furue, Masutaka; Izuhara, Kenji

doi:10.1016/j.alit.2019.12.003

Cited by 43 publications

(37 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The results obtained by real-time PCR as well as the proteome profiler showed a significant decrease in its expression and secretion. Although this cytokine is involved in the process of wound healing, the overproduction of IL24 underlies pro-inflammatory autoimmune diseases such as psoriasis, allergic contact dermatitis, atopic dermatitis, rheumatoid arthritis and inflammatory bowel disease [40,41]. Therefore, a decrease in the secretion of IL24 by MSCs as a result of Vadadustat treatment seems to be a beneficial effect when considering the use of Vadadustat preconditioned MSCs in the treatment of patients with autoimmune diseases.…”

Section: Discussionmentioning

confidence: 99%

Vadadustat, a HIF Prolyl Hydroxylase Inhibitor, Improves Immunomodulatory Properties of Human Mesenchymal Stromal Cells

Zielniok

Burdzińska

Kaleta

et al. 2020

Cells

View full text Add to dashboard Cite

The therapeutic potential of mesenchymal stromal cells (MSCs) is largely attributed to their immunomodulatory properties, which can be further improved by hypoxia priming. In this study, we investigated the immunomodulatory properties of MSCs preconditioned with hypoxia-mimetic Vadadustat (AKB-6548, Akebia). Gene expression analysis of immunomodulatory factors was performed by real-time polymerase chain reaction (real-time PCR) on RNA isolated from six human bone-marrow derived MSCs populations preconditioned for 6 h with 40 μM Vadadustat compared to control MSCs. The effect of Vadadustat preconditioning on MSCs secretome was determined using Proteome Profiler and Luminex, while their immunomodulatory activity was assessed by mixed lymphocyte reaction (MLR) and Culturex transwell migration assays. Real-time PCR revealed that Vadadustat downregulated genes related to immune system: IL24, IL1B, CXCL8, PDCD1LG1, PDCD1LG2, HIF1A, CCL2 and IL6, and upregulated IL17RD, CCL28 and LEP. Vadadustat caused a marked decrease in the secretion of IL6 (by 51%), HGF (by 47%), CCL7 (MCP3) (by 42%) and CXCL8 (by 40%). Vadadustat potentiated the inhibitory effect of MSCs on the proliferation of alloactivated human peripheral blood mononuclear cells (PBMCs), and reduced monocytes-enriched PBMCs chemotaxis towards the MSCs secretome. Preconditioning with Vadadustat may constitute a valuable approach to improve the therapeutic properties of MSCs.

show abstract

Section: Discussionmentioning

confidence: 99%

Vadadustat, a HIF Prolyl Hydroxylase Inhibitor, Improves Immunomodulatory Properties of Human Mesenchymal Stromal Cells

Zielniok

Burdzińska

Kaleta

et al. 2020

Cells

View full text Add to dashboard Cite

show abstract

“…IL-13-induced STAT6 activation upregulates the production of periostin, which promotes allergic inflammation and fibrosis in keratinocytes [142,143]. Periostin stimulates keratinocytes to produce IL-24 [144,145]. IL-24 has two heterodimeric receptors, IL-22Rα/IL-20Rβ and IL-20Rα/IL-20Rβ [146].…”

Section: Downregulation Of Ivl Lor and Flg By Il-4/il-13mentioning

confidence: 99%

“…IL-24 has two heterodimeric receptors, IL-22Rα/IL-20Rβ and IL-20Rα/IL-20Rβ [146]. After ligation with IL-24, both receptors activate JAK1/TYK2 and STAT3, and downregulate FLG expression [144,145] (Figure 3).…”

Section: Downregulation Of Ivl Lor and Flg By Il-4/il-13mentioning

confidence: 99%

Regulation of Filaggrin, Loricrin, and Involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: Pathogenic Implications in Atopic Dermatitis

Furue

2020

IJMS

Self Cite

198

174

View full text Add to dashboard Cite

Atopic dermatitis (AD) is an eczematous, pruritic skin disorder with extensive barrier dysfunction and elevated interleukin (IL)-4 and IL-13 signatures. The barrier dysfunction correlates with the downregulation of barrier-related molecules such as filaggrin (FLG), loricrin (LOR), and involucrin (IVL). IL-4 and IL-13 potently inhibit the expression of these molecules by activating signal transducer and activator of transcription (STAT)6 and STAT3. In addition to IL-4 and IL-13, IL-22 and IL-17A are probably involved in the barrier dysfunction by inhibiting the expression of these barrier-related molecules. In contrast, natural or medicinal ligands for aryl hydrocarbon receptor (AHR) are potent upregulators of FLG, LOR, and IVL expression. As IL-4, IL-13, IL-22, and IL-17A are all capable of inducing oxidative stress, antioxidative AHR agonists such as coal tar, glyteer, and tapinarof exert particular therapeutic efficacy for AD. These antioxidative AHR ligands are known to activate an antioxidative transcription factor, nuclear factor E2-related factor 2 (NRF2). This article focuses on the mechanisms by which FLG, LOR, and IVL expression is regulated by IL-4, IL-13, IL-22, and IL-17A. The author also summarizes how AHR and NRF2 dual activators exert their beneficial effects in the treatment of AD.

show abstract

“…[ 6 – 8 ] Along with the clinical improvement in skin scores and pruritus, dupilumab significantly and progressively reduces and normalizes the elevated expression of Th2 signatures such as Chemokine (C-C motif) ligand (CCL)17, CCL18, CCL22, and CCL26 in the lesional skin of AD. [ 9 , 10 ] Other lesional and blood markers including eosinophils, [ 11 – 13 ] lactate dehydrogenase (LDH), [ 14 ] total immunoglobulin E (IgE), [ 15 ] soluble IL-2 receptor, [ 16 ] CCL27, [ 14 ] IL-13, [ 17 ] IL-22, [ 9 ] IL-24, [ 18 , 19 ] IL-25, [ 20 ] IL-31, [ 21 , 22 ] IL-33, [ 23 ] thymic stromal lymphopoietin (TSLP), [ 24 ] periostin, [ 9 , 25 ] and squamous cell carcinoma antigen-2 (SCCA2) [ 26 , 27 ] are elevated in AD and show substantial correlations with its disease activity.…”

Section: Introductionmentioning

confidence: 99%

Exploration of biomarkers to predict clinical improvement of atopic dermatitis in patients treated with dupilumab

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background: Atopic dermatitis (AD) is a common eczematous skin disorder that profoundly reduces the quality of life due to intractable pruritus. Excellent therapeutic success of the anti-interleukin 4 receptor-α antibody dupilumab in clinical trials and a real-world clinical context indicates the crucial roles of interleukin (IL)-4 and IL-13 in the pathogenesis of AD. Along with the clinical improvement in skin scores and pruritus, dupilumab significantly and progressively reduces and normalizes the upregulated expression of T helper type 2 signatures such as Chemokine (C-C motif) ligand (CCL)17, CCL18, CCL22, and CCL26 in the lesional skin of AD. However, no blood/serum biomarkers are known to predict good or poor outcome in patients with AD treated with dupilumab. Methods: Patients are at least 18 years of age and have moderate-to-severe AD with Eczema Area and Severity Index (EASI) ≥16, Investigator's Global Assessment ≥3, and body surface area ≥10%. We are going to enroll more than 130 subjects from 18 medical facilities. Clinical objective findings will be evaluated by EASI. Subjective symptoms will be assessed by Patient-Oriented Eczema Measure, Numerical Rating Scale for Pruritus (Pruritus-NRS), Skin Comfort-NRS, and Treatment Satisfaction-NRS. We will measure 18 blood/serum biomarkers including % eosinophils in blood cell count, lactate dehydrogenase, total IgE, soluble interleukin 2 receptor, CCL17, CCL18, CCL22, CCL26, CCL27, IL-13, IL-22, IL-24, IL-25, IL-31, IL-33, thymic stromal lymphopoietin, periostin, and squamous cell carcinoma antigen-2. The clinical evaluation and biomarker sampling will be performed at 0, 2, 4, 8, and 16 weeks of dupilumab treatment. We will also perform proteomic analysis (of roughly 300 proteins) of the patients’ sera obtained at 0 and 2 weeks of treatment. The primary endpoint is the association between “baseline levels of 18 biomarkers” and “% change from baseline of EASI at 16 weeks of dupilumab treatment.” Discussion: This is the first clinical trial to explore the biomarkers, including potential proteomic markers, most strongly associated with improvement in EASI in patients with moderate-to-severe AD treated with dupilumab for 16 weeks (B-PAD study). A limitation is that we will only enroll Japanese patients.

show abstract

IL-24: A new player in the pathogenesis of pro-inflammatory and allergic skin diseases

Cited by 43 publications

References 63 publications

Vadadustat, a HIF Prolyl Hydroxylase Inhibitor, Improves Immunomodulatory Properties of Human Mesenchymal Stromal Cells

Vadadustat, a HIF Prolyl Hydroxylase Inhibitor, Improves Immunomodulatory Properties of Human Mesenchymal Stromal Cells

Regulation of Filaggrin, Loricrin, and Involucrin by IL-4, IL-13, IL-17A, IL-22, AHR, and NRF2: Pathogenic Implications in Atopic Dermatitis

Exploration of biomarkers to predict clinical improvement of atopic dermatitis in patients treated with dupilumab

Contact Info

Product

Resources

About