Single-cell RNA sequencing and in vitro validation reveal risankizumab induces anti-inflammatory macrophage polarization in psoriasis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41225578", "kind": "science-record", "revision": 4, "content_hash": "sha256:dc796072cc132598594fd7925353c18e8673fac6791ddeddb4993a3c3096895f", "created_at": "2026-11-01T20:31:15Z", "updated_at": "2026-11-01T22:57:26Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Single-cell RNA sequencing and in vitro validation reveal risankizumab induces anti-inflammatory macrophage polarization in psoriasis.", "doi": "10.1186/s40001-025-03346-0", "pmid": "41225578", "authors": ["Yuan Yuan", "Linzi Li", "Lihong Yang", "Jiyuan Zheng", "Guang Gao", "Ting Tan", "Jing Liu", "Wen Sun"], "journal": "European journal of medical research", "year": 2025, "abstract": "BACKGROUND: Risankizumab was an approved novel drug by Japan for psoriasis, we aimed to explore its underlying therapeutic mechanism through the single-cell RNA sequencing (scRNA-seq) technology.\nMETHODS: ScRNA-seq data (GSE228421) were obtained from the Gene Expression Omnibus (GEO) database. Quality control, normalization, clustering, and cell-type annotation were performed using the R packages Seurat and harmony, together with the CellMarker2.0 database. Differentially expressed genes (DEGs) were identified using the FindMarkers function, and functional enrichment analysis of DEGs was conducted with the ClusterProfiler R package. Cell differentiation trajectories were inferred by pseudo-time analysis using the Monocle2 package. In addition, THP-1 monocytes were differentiated into macrophages and treated with different concentrations of risankizumab. Cell viability was assessed by CCK-8 assay, while cytokine production (TNF-α, IL-1β, IL-6, IL-4, IL-10, and IL-13) was measured using ELISA to evaluate the effects of risankizumab on inflammatory responses and macrophage polarization.\nRESULTS: A total of 97,434 cells were analyzed and divided into eight major clusters. Among them, myeloid cells showed the most significant reduction following risankizumab treatment, suggesting that they may be the primary target of the therapy in psoriasis. Functional enrichment analysis revealed that antibacterial humoral response, antimicrobial humoral response, and keratinization activities in myeloid cells were markedly inhibited. Further analysis identified three macrophage subtypes, and risankizumab treatment was found to promote differentiation of anti-inflammatory IL10⁺ M2 macrophages while reducing IL6⁺ M1 macrophages, thereby contributing to the control of psoriasis. Consistently, in-vitro experiments demonstrated that risankizumab suppressed the production of pro-inflammatory cytokines and enhanced M2 macrophage polarization, confirming its immunomodulatory role.\nCONCLUSIONS: This study reveals that risankizumab exerts its anti-inflammatory effects by inhibiting M1-type and promoting M2-type macrophage polarization, thereby elucidating its key mechanism for treating psoriasis and providing theoretical support for novel immunotherapy targets.", "claims": [{"id": "claim-method", "statement": "The Shapiro–Wilk test results determined the application of the Wilcoxon rank-sum test and Student’s t test for comparing the two groups. Spearman’s coefficient was utilized to conduct the correlation analysis. In addition, all in vitro experiments were performed in triplicate, with results expressed as mean ± SD. Comparisons between two groups were performed using Student's t test, while comparisons among multiple groups were conducted using one-way ANOVA.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41225578", "locator": "sections[10] \"Statistical analysis\" paragraph 2", "quote": "The Shapiro–Wilk test results determined the application of the Wilcoxon rank-sum test and Student’s t test for comparing the two groups. Spearman’s coefficient was utilized to conduct the correlation analysis. In addition, all in vitro experiments were performed in triplicate, with results expressed as mean ± SD. Comparisons between two groups were performed using Student's t test, while comparisons among multiple groups were conducted using one-way ANOVA."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and/or analyzed during the current study are available in the [GSE228421] repository, [https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE228421].", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41225578", "locator": "sections[24] \"Availability of data and materials\" paragraph 2", "quote": "The datasets generated and/or analyzed during the current study are available in the [GSE228421] repository, [https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE228421]."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Risankizumab treatment decreased IL6⁺ M1 macrophages from 32.88% to 23.32% while increasing IL10⁺ M2 macrophages from 24.92% to 35.07%.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:41225578", "locator": "sections[15] \"Risankizumab decreased the M1 and increased the M2 macrophages for psoriasis controlling\" paragraph 2", "quote": "Interestingly, we found that the proportion of IL6 + M1 macrophage was decreased from the 32.88% to 23.32% after risankizumab treatment, while on the contrary, the IL10 + M2 macrophage was increased from the 24.92% to 35.07% (Fig. 4C), and the M2 marker genes such as the CD209, TGFB1 and IL10 were significantly overexpressed in the IL10 + M2 macrophage (Fig. 4D), suggesting the risankizumab treatment controlled the development of psoriasis through decreasing the pro-inflammatory macrophages M1 and increasing the anti-inflammatory macrophages M2 numbers."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "Risankizumab treatment decreased IL6⁺ M1 macrophages from 32.88% to 23.32% while increasing IL10⁺ M2 macrophages from 24.92% to 35.07%.", "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:41225578"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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