Journal: Psoriasis: Targets and Therapy

Article Title: Indole-3-Lactic Acid Attenuates IMQ-Induced Psoriasiform Dermatitis in Mice via AhR-Dependent Suppression of IL-17A

doi: 10.2147/PTT.S585731

Figure Lengend Snippet: Pharmacologic AhR inhibition counteracts the effects of oral ILA in IMQ-induced PsD. ( A ) Experimental scheme. Mice received daily oral ILA beginning day −2 relative to IMQ application. A subset was co-treated with the AhR antagonist CH-223191 (AhRi) by daily intraperitoneal injection.Tissues were collected on day 5. ( B ) Representative ear photographs, ear thickness and Psoriasis Severity Index (PSI) at endpoint. ( C ) Representative H&E-stained ear sections. ( D ) Quantification of epidermal thickness and Munro microabscesses per section. ( E ) Representative Ki-67 IHC of epidermis. Scale bars, 100μm. ( F ) Spleen index and total cellularity of cervical skin-draining lymph nodes (cLNs). ( G ) Flow-cytometry analysis of cLNs. Left: representative plots; right: frequencies of IL-17A⁺ CD3⁺ T cells in CD3+gate and IL-17A⁺ γδ T cells in TCRγδ+ gate. ( H ) Neutrophils in ear skin. Left: representative plots (neutrophils defined as CD11b⁺Ly6G⁺); right: frequency within live CD45⁺ cells and absolute counts per ear. ( I ) RT-PCR of ear tissue showing relative mRNA levels of psoriasis-associated genes. Scale bars: C and E, 100 μm.Data are presented as mean ± SEM, with each dot representing one mouse. Statistical comparisons between two groups used two-tailed unpaired t-tests. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001.

Article Snippet: Where indicated, the AhR antagonist CH-223191 (MedChemExpress) was given by intraperitoneal injection at 10 mg kg −1 day −1 , commencing 2 days before and continuing during IMQ exposure.

Techniques: Inhibition, Injection, Staining, Flow Cytometry, Reverse Transcription Polymerase Chain Reaction, Two Tailed Test

Journal: Psoriasis: Targets and Therapy

Article Title: Indole-3-Lactic Acid Attenuates IMQ-Induced Psoriasiform Dermatitis in Mice via AhR-Dependent Suppression of IL-17A

doi: 10.2147/PTT.S585731

Figure Lengend Snippet: ILA inhibits IL-17A production by γδ T cell in vitro. ( A ) Il17a mRNA in cervical lymph node (cLN) cells after 12 h stimulation with IL-23 (50 ng/mL) + IL-1β (10 ng/mL) (Cyto) in the absence or presence of indole-3-lactic acid (ILA) and/or the AhR antagonist CH-223191 (AhRi). ( B ) Representative intracellular cytokine staining plots showing IL-17A–producing γδ T cells within the CD3⁺ TCRγδ⁺ gate after 24 h under the indicated conditions. ( C ) Quantification of (left) the frequency (%) of IL-17A⁺ γδ T cells, (middle) mean fluorescence intensity (MFI) of IL-17A within IL-17A⁺ γδ T cells, and (right) total fluorescence intensity (TFI) of IL-17A across the γδ T-cell gate (sum signal per sample).Bars show mean ± SEM with individual data points (each dot = one biological replicate). Group comparisons used one-way ANOVA with Šidák post hoc tests; ns, not significant; *, P < 0.05; **, P < 0.01,****p < 0.0001.

Article Snippet: Where indicated, the AhR antagonist CH-223191 (MedChemExpress) was given by intraperitoneal injection at 10 mg kg −1 day −1 , commencing 2 days before and continuing during IMQ exposure.

Techniques: In Vitro, Staining, Fluorescence

Journal: Psoriasis: Targets and Therapy

Article Title: Indole-3-Lactic Acid Attenuates IMQ-Induced Psoriasiform Dermatitis in Mice via AhR-Dependent Suppression of IL-17A

doi: 10.2147/PTT.S585731

Figure Lengend Snippet: ILA inhibits inflammation of keratinocytes with limited involvement of AhR. ( A ) HaCaT cells were stimulated with IL-17A + TNF-α (Cyto) in the presence or absence of ILA. Relative mRNA abundance of S100A7, S100A8, CCL20, CXCL1, CXCL2, IL1B, and IL6 is shown ( B ) Effect of AhR antagonism: Cells were treated with cytokines plus AhR inhibitot CH-223191 (AhRi) and/or ILA. In the presence of ILA, CH-223191 produced an observable upward shift for S100A7 and S100A8 compared with cytokines + ILA, with minimal change for CCL20, CXCL1, CXCL2, and IL6 under the same comparison. Data are presented as mean ± SEM, with each dot representing one biological replicate. ( A ) statistical tests for multi-group comparisons were performed by one-way ANOVA with Dunnett’s test compared to Cyto group, ( B ) statistical tests for multi-group comparisons were performed by one-way ANOVA with Sidak’s test comparing selected groups.*p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. ns, not significant.

Article Snippet: Where indicated, the AhR antagonist CH-223191 (MedChemExpress) was given by intraperitoneal injection at 10 mg kg −1 day −1 , commencing 2 days before and continuing during IMQ exposure.

Techniques: Produced, Comparison

Journal: Psoriasis: Targets and Therapy

Article Title: Indole-3-Lactic Acid Attenuates IMQ-Induced Psoriasiform Dermatitis in Mice via AhR-Dependent Suppression of IL-17A

doi: 10.2147/PTT.S585731

Figure Lengend Snippet: Lactobacillus reuteri mitigates IMQ-induced PsD and requires AhR signaling. ( A ) Experimental scheme for oral L. reuteri treatment. Mice received daily L. reuteri beginning day −14 and throughout IMQ treatment, tissues were collected on day 5. ( B ) Representative ear photographs, ear thickness and Psoriasis Severity Index (PSI) at endpoint. ( C ) Representative H&E-stained ear sections. Quantification of epidermal thickness and Munro microabscesses per section. ( D ) Spleen index at endpoint. ( E ) Representative flow-cytometry plots of ear single-cell suspensions, neutrophils were defined as CD11b⁺Ly6G⁺in CD45+ gate.Quantification of percentage and absolute counts of neutrophils per ear. ( F ) Correlation of fecal ILA concentration with ear thickness (left) and neutrophil frequency in ear skin (right) from IMQ-treated mice receiving vehicle or L. reuteri . Lines indicate linear fit with Pearson r and p values. ( G ) Experimental scheme for AhR blockade during L. reuteri treatment. Mice received daily oral L. reuteri starting day −14 and were co-treated with CH-223191 (AhRi) or vehicle beginning day-2, tissues were collected on day 5. ( H ) Representative ear photographs, ear thickness and PSI. ( I ) Representative H&E-stained ear sections and ( J ) quantification of epidermal thickness and Munro microabscesses. Scale bars: C and I, 100 μm. Data are presented as mean ± SEM.Statistical comparisons between two groups used two-tailed unpaired t-tests,statistical tests for multi-group comparisons were performed by one-way ANOVA with Dunnett’s test compared to IMQ+vehicle group. Pearson correlation coefficient was utilized for correlation. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001, ns, not significant.

Article Snippet: Where indicated, the AhR antagonist CH-223191 (MedChemExpress) was given by intraperitoneal injection at 10 mg kg −1 day −1 , commencing 2 days before and continuing during IMQ exposure.

Techniques: Staining, Flow Cytometry, Single Cell, Concentration Assay, Two Tailed Test