Journal: PLOS One

Article Title: Clinical proof of concept for small molecule mediated inhibition of IL-17 in psoriasis

doi: 10.1371/journal.pone.0341049

Figure Lengend Snippet: (A) Inhibition of IL-17 bioactivity as secreted by human TH17 cells and assayed by a reporter cell assay. Dotted lines represent positive and negative assay controls. 1 representative of 7 experiments with different donors is shown. The error bars represent the SEM. (B, C) Evaluation of DC-806 in rat CIA. Rats were randomized on Day 11 and dosed as indicated. Daily measurements of ankle thickness (B) and terminal measurement of footpad weights (C) were used as efficacy readouts. (D) Preclinical evaluation of DC-806 serum levels. PK sampling for exposure determination was performed on Days 11, 16, at 1 and 12 hours post dose. The dotted lines represent the uncorrected IC 50 for rat IL-17AA and rat IL-17AF as listed in . The dashed line represents the LLQ of the quantification assay. All error bars represent the SEM. * P < 0.05; ** P < 0.01; *** P < 0.001; **** P < 0.0001. Abbreviations : anti-F, anti-IL-17F; BID, twice daily; CIA, collagen-induced arthritis; Dex, dexamethasone; IC 50 , half-maximal inhibitory concentration; IL-17, interleukin-17; LLQ, lower limit of quantification; PK, pharmacokinetic; QD, once daily; SEM, standard error of mean; TH17, T-helper 17.

Article Snippet: Serum IL-17A level was measured using Quantikine ® High Sensitivity (HS) Human IL-17 Immunoassay kit #HS170 (R&D Systems), which mostly detects IL-17AA with approximately 3% cross-reactivity to IL-17AF [ ].

Techniques: Inhibition, Sampling, Concentration Assay

Journal: PLOS One

Article Title: Clinical proof of concept for small molecule mediated inhibition of IL-17 in psoriasis

doi: 10.1371/journal.pone.0341049

Figure Lengend Snippet: Graph detailing the group mean ± SD DC-806 plasma concentration by 200 mg BID (green circle) and 800 mg BID (blue diamond) groups on a semilogarithmic scale through Study Day 29. PK in psoriasis patients was comparable to healthy volunteer PK, with consistent trough levels over 28 days after achieving steady state around Day 3. The dotted line represents IC 50 for recombinant human IL-17AA, as obtained using HEK-blue IL-17 cell-based assay . PK Concentration Analysis Set. Abbreviations : BID, twice daily; HEK: human embryonic kidney; IC 50 , half-maximal inhibitory concentration; IL-17, interleukin-17; PK, pharmacokinetic; SD, standard deviation.

Article Snippet: Serum IL-17A level was measured using Quantikine ® High Sensitivity (HS) Human IL-17 Immunoassay kit #HS170 (R&D Systems), which mostly detects IL-17AA with approximately 3% cross-reactivity to IL-17AF [ ].

Techniques: Clinical Proteomics, Concentration Assay, Recombinant, Cell Based Assay, Standard Deviation

Journal: PLOS One

Article Title: Clinical proof of concept for small molecule mediated inhibition of IL-17 in psoriasis

doi: 10.1371/journal.pone.0341049

Figure Lengend Snippet: (A–C) DC-806 demonstrated biological effects as evidenced by dose-dependent responses of biomarkers of interest compared to placebo. Blue diamonds represent the 800 mg BID group; Green circles represent the 200 mg BID group; Black triangles represent the placebo group. (A) Change in mean ± SEM serum IL-17AA levels from time of first dose through 28 days post first dose. The dotted line represents low limit of quantification of the assay. (B) Change in mean ± SEM serum BD-2 levels from time of first dose through 28 days thereafter. *Except on Day 28 when n = 10; **Except on Day 28 when n = 9. (C) Change in mean ± SEM plasma IL-19 levels from time of first dose through 28 days post first dose. The dotted line represents normalization value of 21 pg/mL. PD Biomarker Analysis Set. Abbreviations: BD-2, beta defensin-2; BID, twice daily; BL, baseline; IL-17, interleukin-17; PASI, psoriasis area and severity index; PD, pharmacodynamic; SEM, standard error of mean.

Article Snippet: Serum IL-17A level was measured using Quantikine ® High Sensitivity (HS) Human IL-17 Immunoassay kit #HS170 (R&D Systems), which mostly detects IL-17AA with approximately 3% cross-reactivity to IL-17AF [ ].

Techniques: Clinical Proteomics, Biomarker Discovery

Journal: Nature Communications

Article Title: Microbiome-derived bile acid signatures in early life and their association with islet autoimmunity

doi: 10.1038/s41467-025-66619-6

Figure Lengend Snippet: a Schematic of the Th17 and iTreg differentiation protocol for primary human naïve CD4 + CD25 − T cells isolated from the umbilical cord blood of healthy neonates. CD4 + CD25 − T cells were activated with anti-CD3/anti-CD28 and differentiated into Th17 or iTreg cells in the presence of corresponding cytokines for 3 days. DMSO control or conjugated bile acids (Asn-UDCA, Ser-CDCA, Tyr-CDCA, and unconjugated UDCA) at 100 µM were added on day 0 of differentiation. Illustrations in a panel were created with BioRender.com (licensed). b – e IL-17a secretion in the supernatant of Th17 cultures treated with Asn-UDCA ( b ), Ser-CDCA ( c ), Tyr-CDCA ( d ), and UDCA ( e ) was quantified on day 3 of differentiation from four biological replicates using ELISA. f – i . Intracellular Foxp3 protein expression in iTregs cultured with Asn-UDCA ( f ), Ser-CDCA ( g ), Tyr-CDCA ( h ), or UDCA ( i ) was assessed on day 3 of differentiation by flow cytometry. Geometric mean fluorescence intensity (MFI) values are shown for six biological replicates. Statistical significance was determined using a paired, two-tailed Student’s t-test. Illustrations were Created in BioRender. Hirvonen, K. (2025) https://BioRender.com/5s3bnh7 . Asn–UDCA asparagine–ursodeoxycholic acid, Ser–CDCA serine–chenodeoxycholic acid, Tyr–CDCA tyrosine–chenodeoxycholic acid, UDCA ursodeoxycholic acid.

Article Snippet: To study the effect of MCBAs on human Th17 and iTreg cell differentiation, 100 μM of either Asn-UDCA, Ser-CDCA, Tyr-CDCA, or UDCA (in DMSO), and DMSO as a control, were added to the Th17 and iTreg cell culture media at day 0, and cultured for 72 h. After differentiation, secreted IL-17a levels were determined from Th17 cell-culture supernatants at 72 h using the human IL-17a DuoSet ELISA kit (R&D Systems, Cat# DY317-05, DY008).

Techniques: Isolation, Control, Enzyme-linked Immunosorbent Assay, Expressing, Cell Culture, Flow Cytometry, Fluorescence, Two Tailed Test