---
title: "Fatty Acid–Binding Protein 4 Inhibition and Psoriasis: Article Content Not Provided"
id: "frontiers-in-immunology-16-inhibition-of-fatty-acid-binding-protein-4-alleviates-psoriasis-like-skin"
canonical_url: "https://medichelpline.com/clinical-feed/frontiers-in-immunology-16-inhibition-of-fatty-acid-binding-protein-4-alleviates-psoriasis-like-skin"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "Frontiers in Immunology"
source_url: "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1830077"
published_at: "2026-08-03T00:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Fatty Acid–Binding Protein 4 Inhibition and Psoriasis: Article Content Not Provided
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/frontiers-in-immunology-16-inhibition-of-fatty-acid-binding-protein-4-alleviates-psoriasis-like-skin
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** Frontiers in Immunology
- **Source URL:** [Original Journal Publication](https://www.frontiersin.org/articles/10.3389/fimmu.2026.1830077)
- **Published At:** 2026-08-03T00:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The source page and metadata were accessible, but the full research article text and results were not present in the provided SOURCE JINA body. - The article title indicates a focus on **fatty acid-binding protein 4 (FABP4)**, psoriasis-like skin inflammation, and modulation of macrophage polarization, but no abstract, methods, results, or conclusions were included in the source content. - Because the body text and data were not reported, specific experimental design, sample size, models (in vivo/in vitro), statistical outcomes, molecular findings, and any stated mechanisms could not be extracted or verified from the source. - No numerical results, effect sizes, p values, or authors’ interpretations were available in the provided file; therefore causal claims, therapeutic recommendations, and translational implications cannot be summarized from the source. - The absence of article content prevents confirmation of key details such as whether FABP4 inhibition was pharmacologic or genetic, which macrophage markers or polarization states were measured, or whether psoriasis-like phenotypes were assessed in animals, human tissue, or cell culture. - For clinicians and researchers, the missing content means the primary evidence base referenced by the title cannot be evaluated; the original Frontiers in Immunology article should be consulted directly for methods, data, and conclusions. - Where the source lacks detail, this rewrite explicitly states that those specifics were not reported in the provided content and avoids inventing data or unverified interpretations. - Readers are advised to retrieve the full article (Frontiers in Immunology) or contact the publisher/author for the complete manuscript to assess clinical relevance and methodological rigor.
## Clinical Analysis & Structured Key Points
Frontiers | Inhibition of fatty acid-binding protein 4 alleviates psoriasis-like skin inflammation by modulating macrophage polarization ORIGINAL RESEARCH article Front. Immunol. , 03 August 2026 Sec. Inflammation Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1830077 Published in Frontiers in Immunology Inflammation 7 impact factor 11.3 citescore Part of a Research Topic Immunology of Skin Health and Disease Submission open 32k views 20 articles Editor & Reviewers Edited by E S Emanuele Scala Reviewed by J C Jiangluyi Cai K N Katarzyna Nazimek M M Mirco Mastrangelo Outline Figures and Tables Figure 1 View in article Figure 2 View in article Figure 3 View in article Figure 4 View in article Figure 5 View in article Figure 6 View in article Figure 7 View in article ORIGINAL RESEARCH article Front. Immunol. , 03 August 2026 Sec. Inflammation Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1830077 Inhibition of fatty acid-binding protein 4 alleviates psoriasis-like skin inflammation by modulating macrophage polarization B M Bo Mi Kang 1,2,3 † H S Hyun Seung Choi 4,5 † B R Bo Ri Kim 1,2 S W Sang Woong Youn 1,2 H J Hyun Jung Kwon 6 J L Jin-Ku Lee 7,8 C S Christine Suh-Yun Joh 4 H J Hyo Jeong Nam 4 S J Soyoung Jeong 4 H W Hyun Woo Kim 4 J E Jeong Eun Kim 9,10 T K Tae-Gyun Kim 11,12 H J Hyun Je Kim 4,5,13 * +5 more C W Chong Won Choi 1,2,3 * 1. Department of Dermatology, Seoul National University College of Medicine, Seoul, Republic of Korea 2. Department of Dermatology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea 3. Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Republic of Korea 4. Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea 5. Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea 6. Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Republic of Korea 7. Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea 8. Department of Anatomy and Cell Biology, Seoul National University College of Medicine, Seoul, Republic of Korea 9. Department of Dermatology, Hanyang University College of Medicine, Seoul, Republic of Korea 10. Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul, Republic of Korea 11. Department of Dermatology, Severance Hospital, Cutaneous Biology Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea 12. Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Republic of Korea 13. Interdisciplinary Program in Artificial Intelligence (IPAI), Seoul National University, Seoul, Republic of Korea See more Article metrics View details Abstract Fatty acid-binding proteins (FABPs) are intracellular lipid chaperones that regulate gene expression by controlling lipid trafficking within subcellular organelles. Among them, FABP4 is primarily expressed in adipocytes and macrophages and has been implicated in inflammatory responses in adipose tissue; however, its role in skin inflammation remains poorly understood. Here, we investigated the immunomodulatory role of FABP4 using human psoriatic skin samples, single-cell RNA sequencing, and an imiquimod-induced mouse model of psoriasis. We further employed pharmacologic inhibition and genetic modulation of FABP4 to assess its effects on macrophage polarization, along with transcription factor regulon analyses to identify downstream regulatory mechanisms. FABP4 was highly expressed in macrophages infiltrating psoriatic skin, and in vivo pharmacological inhibition of FABP4 attenuated psoriasiform skin inflammation and shifted macrophage phenotypes, suppressing M1-associated features while promoting CD206-expressing alternatively activated macrophages. For mechanistic insights, we examined the regulon activity of transcription factors associated with macrophage polarization in psoriatic skin and identified an association between PPARG and macrophage polarization; our in vivo and in vitro experiments further demonstrated that FABP4 inhibition restored PPARG expression and activity in psoriasis mice, which was decreased by imiquimod application. Overall, our study demonstrated that FABP4 plays a critical role in skin inflammation by modulating macrophage polarization through PPARG regulation, suggesting that targeting FABP4 may represent a potential therapeutic strategy for psoriasis and other inflammatory skin diseases. Introduction Psoriasis is a common chronic inflammatory disease. Although psoriasis involves mainly the skin, nails, and joints, previous studies have revealed an association of psoriasis with inflammatory conditions in other organs including inflammatory arthritis, Crohn’s disease, obesity, and metabolic syndrome ( 1 , 2 ). Among them, the association between obesity and psoriasis has received increased attention: patients with psoriasis have a higher risk of obesity, with the risk increasing with psoriasis severity ( 3 , 4 ). Additionally, an inverse relationship was also revealed, that is, obese people have a higher risk of psoriasis ( 3 , 5 ). The association between psoriasis and obesity has been attributed to common inflammatory pathways and metabolic abnormalities ( 2 ). Recent clinical and in-vivo animal studies found that abnormalities in fatty acid metabolism may play a role in the pathogenesis of psoriasis and its comorbidities ( 2 , 6 , 7 ). For example, in an imiquimod-induced mouse model fed a high-fat diet, increased fatty acids aggravated skin inflammation ( 6 ). Regarding the link between fatty acids and inflammation, previous studies have revealed that fatty acids regulate inflammation by modulating immune cells ( 8 ). Among them, myeloid cells have been identified as primarily responsible for increasing the inflammatory response and augmenting the activation of keratinocytes in psoriatic mice ( 9 ). These results strongly suggest an association between psoriasis, dysregulated fatty acid metabolism, and macrophages. Fatty acids act as signaling molecules in inflammatory responses and as an energy source for cells ( 10 , 11 ). When lipids enter cells, fatty acid-binding protein (FABP), an intracellular lipid chaperone, controls the trafficking of lipids in subcellular organelles, thereby regulating gene expression in the nucleus ( 10 , 12 ). FABP4 is an isoform of FABP highly expressed in adipocytes and macrophages ( 13 , 14 ). Crucially, previous studies have identified FABP4 not merely as a lipid chaperone but as a central regulator at the interface of lipid metabolism and inflammation, specifically in macrophages ( 15 , 16 ). In macrophages which abundantly express FABP4, activation of FABP4 plays a major role in macrophage polarization toward the pro-inflammatory M1 subtype by coupling intracellular fatty acid trafficking with the NF-κB and JNK signaling pathways ( 15 , 17 , 18 ). Notably, the role of FABP4 in the regulation of inflammatory reactions has also been demonstrated in animal models and human research ( 19 – 21 ). Considering the increased expression of FABP4 in patients with psoriasis, especially in obese patients ( 22 ), the association between macrophage differentiation, FABP4, and fatty acids in psoriasis can be inferred. Emerging studies have illustrated that patients with psoriasis exhibited elevated FABP4 levels; however, the mechanism by which FABP4 contributes to psoriasis development remains unexplored ( 23 ). Given that macrophages are key effector cells that infiltrate psoriatic lesions and orchestrate local inflammation, we hypothesized that FABP4 might link dysregulated lipid metabolism to psoriatic skin inflammation specifically through macrophage modulation. To explore this, we first utilized single-cell RNA sequencing (scRNA-seq) to profile human psoriatic skin, revealing a distinct macrophage polarization imbalance skewed toward a proinflammatory M1 phenotype. To elucidate the upstream regulatory mechanisms governing this polarization, we performed transcription factor regulon analysis and identified peroxisome proliferator-activated receptor gamma (PPARG), which is known to be closely related to FABP4, as a master transcription factor driving the anti-inflammatory M2 macrophage program. Based on these clinical and bioinformatic findings, we investigated the role of FABP4 in an imiquimod-induced psoriasis mouse model and in vitro macrophage cultures. Our study demonstrated that both pharmacological inhibition and genetic silencing of FABP4 effectively alleviated skin inflammation by restoring PPARG protein stability and activity, which in turn recalibrated macrophage polarization toward the resolving M2 phenotype. Materials and methods Animals For the in vivo study, 7-week-old female C57BL/6 mice were purchased (Orient Bio Inc, Gyeonggi, Republic of Korea). Mice were housed in a specific pathogen-free facility with sterile food and water ad libitum and were acclimatized for at least 1 week before being used in the experiments. All animal experiments were approved by the Animal Experimental Ethics Committee of our hospital (BA-2208-349-003-04). All procedures were conducted in accordance with the institutional guidelines for the care and use of laboratory animals and complied with the ARRIVE guidelines. Induction of imiquimod-induced psoriasis-like skin inflammation in mice A daily topical dose of 62.5 mg of 5% imiquimod cream (Aldara ® ; 3M Pharmaceuticals, Maplewood, MN, USA) was applied to the shaved backs and ears of 8-week-old female C57BL/6 mice for five consecutive days. BMS-309403, a FABP4 inhibitor, was dissolved in DMSO as a stock solution and diluted in PBS immediately before use. Vehicle and FABP4 inhibitor (0.5 mg/kg and 1 mg/kg; BMS-309403, Medchemexpress LLC, Monmouth Junction, NJ, USA) were administered by intraperitoneal injection into mice on days 2 and 4. During the experiment, the severity of psoriasis-like skin inflammation (PASI score) was assessed using the psoriasis area and severity index (PASI), which is calculated by summing the scores for erythema, scaling, and thickness in the psoriasis area. In addition, ear thickness was measured once daily at the same time point before the daily application of imiquimod using a digital caliper (Mitutoyo, Japan) to assess gross inflammatory changes. On day 6, the mice were euthanized via CO 2 inhalation, and back and ear skin tissues were collected for histological analysis, quantitative reverse transcription PCR (RT-qPCR), and flow cytometric analysis. According to IACUC ethical standards, if a side effect occurred, such as a decrease in feed intake or a weight loss of >20% of normal body weight, the experiment was terminated. However, no changes in the animals were observed that could be attributed to these experiments. Immunofluorescence and histopathologic analyses For histopathologic analysis, the back and ear skin of mice were harvested and fixed in 4% paraformaldehyde solution. Paraffin-embedded skin tissue sections were deparaffinized and rehydrated using an ethanol series. The sections were stained with hematoxylin and eosin (H&E). A slide scanner (PANNORAMIC 250 Flash III, 3DHISTECH, Budapest, Hungary) was used to acquire the images for histopathological analysis. To evaluate the severity of psoriasis-like skin inflammation, we measured the epidermal thickness using the ImageJ software. Ear thickness measured by digital caliper (Mitutoyo, Japan) reflects overall tissue swelling in vivo , whereas epidermal thickness assessed from H&E-stained sections represents histological changes at the tissue level. For the immunofluorescence analysis, tissue samples were obtained from patients who presented to Seoul National University Bundang Hospital and underwent skin biopsies. This study was approved by the Institutional Review Board of Seoul National University Bundang Hospital (B-2309-851-303). First, the paraffin-embedded tissue sample was cut at 4 µm thickness and deparaffinized. The sections were subjected to heat-induced antigen retrieval in 0.01 M citrate buffer (pH 6.0; Thermo Fisher Scientific, Waltham, MA, USA). After antigen retrieval, the sections were blocked with a blocking solution (Epredia UltraVision Protein Block, #TA-125-PBQ, Thermo Fisher Scientific) for 30 min at 25 °C and incubated with the primary antibodies in a humidified chamber at 4 °C overnight. Primary antibodies against FABP4 were purchased from Thermo Fisher Scientific (1:100 dilution; PA5-30591). For human skin sections, CD68 was used as a macrophage marker, and primary antibodies against CD68 were purchased from Abcam (1:100 dilution; ab201340). For mouse skin sections, F4/80 was used as a macrophage marker, and primary antibodies against F4/80 were purchased from Invitrogen (1:100 dilution; MA1-91124; Waltham, MA, USA). After washing in phosphate-buffered saline (PBS), the sections were incubated with secondary antibody (Alexa Fluor 488 and 594, 1:200 dilution; Invitrogen, Waltham, MA, USA) at 25 °C for 1 h. Last, the sections were stained with 4′-6-diamidino-2-phenylindole dihydrochloride (Thermo Fisher Scientific) at 25 °C for 10 min. The samples were mounted using Faramount Aqueous Mounting Medium (Dako, Santa Clara, CA, USA). Confocal laser scanning microscopy (LSM710; Carl Zeiss, Oberkochen, Germany) was used to acquire the images for immunofluorescence analysis. Quantitative RT-PCR After harvesting, the mouse skin samples were homogenized with a Bioprep-6 homogenizer (Allsheng, Hangzhou, China). Then, total RNA was isolated using Trizol reagent (Invitrogen) according to the manufacturer’s instructions. cDNA was synthesized from 5.0 µg of extracted total RNA using the First Strand cDNA Synthesis Kit (Thermo Fisher Scientific). Subsequently, the mRNA expression level was evaluated using the 7500 Real Time PCR system (Applied Biosystems, Foster City, CA, USA) and AccuPower ® 2X GreenStar™ qPCR Master Mix (Bioneer, Daejeon, Korea). The 2 -ΔΔCq method was used to determine the relative changes in the expression of each target gene. The expression of each gene was normalized to the expression of the Gapdh gene. The primer sequences for each gene are listed in Supplementary Table 1 . Assessment of M1/M2 polarization RAW 264.7 cells were seeded at a density of 1 × 10 6 cells/well in 60-mm cell culture dishes. Cells were treated with vehicle (0.1% DMSO), lipopolysaccharide (LPS, 5 μg/mL) or LPS (5 μg/mL) + FABP4 inhibitor (0.1, 1 μM) for 24 h. For evaluating M1/M2 polarization using qPCR, total RNA was isolated from the cell lysates using the Trizol reagent. For flow cytometry analysis, RAW 264.7 cells were stained with monoclonal antibodies against mouse CD206 (FITC, C068C2; BioLegend, San Diego, CA, USA) and CD11c (PerCP, N418, BioLegend). Cells were first gated based on forward and side scatter (FSC/SSC) to exclude debris. Doublets were excluded by FSC-A versus FSC-H gating. Viable cells were selected based on morphological parameters. CD11c + and CD206 + populations were quantified within the singlet gate. Flow cytometric analyses were performed using a FACSymphony™ A1 Cell Analyzer (BD Biosciences). Data were analyzed using FlowJo software (BD Biosciences). Flow cytometric analysis of macrophage polarization For flow cytometric analysis of mouse skin samples, ear skin tissues were harvested on day 6 and processed into single-cell suspensions. Briefly, the tissues were minced into small pieces and enzymatically digested with collagenase, DNase I, and trypsin to dissociate the skin tissue into single cells. The digested tissues were mechanically dissociated and sequentially filtered through 100-μm and 40-μm cell strainers to remove undigested tissue fragments and debris. Cells were then washed with PBS containing 2% fetal bovine serum. Before antibody staining, cells were incubated with TruStain FcX™ PLUS anti-mouse CD16/32 antibody (clone S17011E; BioLegend, San Diego, CA, USA) to minimize nonspecific Fc receptor-mediated binding. Dead cells were excluded using Zombie Violet™ Fixable Viability Dye (BioLegend, San Diego, CA, USA), according to the manufacturer’s instructions. Cells were subsequently stained with fluorochrome-conjugated monoclonal antibodies against mouse CD45 APC/Cyanine7 (clone 30-F11; BioLegend), F4/80 APC (clone BM8; BioLegend), CD11c PerCP (clone N418; BioLegend), and CD206 FITC (clone C068C2; BioLegend). To analyze macrophage polarization, cells were first gated based on forward scatter and side scatter to exclude debris, followed by doublet exclusion using FSC-A versus FSC-H. Viable cells were then selected by excluding Zombie Violet-positive dead cells. CD45 + immune cells were subsequently gated, and macrophages were identified as F4/80 + cells within the CD45 + population. CD11c + and CD206 + populations were then quantified within the CD45 + F4/80 + macrophage gate and interpreted as M1-associated/pro-inflammatory and M2-associated macrophage populations, respectively. Flow cytometric analyses were performed using a FACSymphony™ A1 Cell Analyzer, and data were analyzed using FlowJo software. Immunoblotting Skin tissue samples and cultured cells, following treatment with the FABP4 inhibitor at the indicated concentrations, were homogenized and lysed in radioimmunoprecipitation assay (RIPA) buffer containing a protease (Roche, Basel, Switzerland) and phosphatase (GenDEPOT, Baker, TX, USA) inhibitor mixture. Total cell lysates and tissue extracts were separated by 10% sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and transferred to polyvinylidene fluoride (PVDF) membranes. The membranes were blocked with 5% skim milk (Difco skim milk, 232100, BD Biosciences) in PBS containing 0.1% Tween 20 (PBST) for 1 h at 25 °C and probed with PPARG (1:1000 dilution, PA3-821A; Invitrogen), lamin B (1:1000 dilution, D4Q4Z; Cell Signaling Technology, Danvers, MA, USA);, and β-actin (1:1000 dilution, 13E5; Cell Signaling Technology) primary antibodies. Horseradish peroxidase-conjugated goat anti-rabbit antibody was used as a secondary antibody (1:10000, 32460; Invitrogen). The bands were visualized using the enhanced chemiluminescence detection system (Bio-Rad Laboratories, Hercules, CA, USA). Gene silencing via siRNA transfection RAW 264.7 cells were seeded before transfection to reach approximately 50% confluence at the time of transfection. Cells were transfected with the negative control (scrambled) siRNA or FABP4-specific siRNA using Lipofectamine RNAiMAX(13778; Invitrogen). The control scrambled siRNA was obtained from Bioneer. The siRNA sequences targeting FABP4 were as follows: Forward 5’-CAU UGA ACU CUA CAA CAU U-3’; Reverse 5’-AAU GUU GUA GAG GAG UUC AAU G-3’. Briefly, siRNA and RNAiMAX were separately diluted in Opti-MEM (Invitrogen), combined, and incubated at room temperature for 20 min to allow complex formation. The siRNA-lipid complexes were then added to cells. After 6 hours of transfection, the culture medium was replaced and the cells were incubated at 37 °C in a CO 2 incubator. After 24 hours, RAW 264.7 cells were lysed using TRIzol reagent (Invitrogen) according to the manufacturer’s instructions for subsequent RNA extraction. PPARG antagonism treatment To pharmacologically antagonize PPARG, cells were seeded and cultured to reach approximately 80% confluence and treated with GW9662 (MedChemExpress, HY-16578R) or a FABP4 inhibitor. GW9662 was diluted in serum-free DMEM medium immediately before use. An equivalent volume of vehicle (DMSO) was added to the control group. For experiments assessing the role of PPARG in macrophage polarization, GW9662 was co-administered with LPS and the FABP4 inhibitor, as specified in the figure legends. After 24 hours, cells were harvested and processed for qPCR analysis. Cell culture RAW 264.7 cells w
## Related Clinical Research

- [Shared genetic architecture and spatial cellular mapping of psoriasis and metabolic syndrome](https://medichelpline.com/clinical-feed/plos-one-9-shared-genetic-basis-and-spatial-cellular-atlas-of-psoriasis-and-metabolic.md)
- [GLP-1 Receptor Agonists in Rheumatic Disease: Mechanisms, Evidence, and Clinical Considerations](https://medichelpline.com/clinical-feed/pubmed-42706128.md) (DOI: 10.3760/cma.j.cn112137-20260312-00692)
- [Climate change worsens health for people with chronic illness](https://medichelpline.com/clinical-feed/stat-news-1-opinion-climate-change-is-making-people-with-chronic-illness-even-sicker.md)
- [MicroRNAs in Immune-Related Diseases: Mechanisms, Functions and Therapeutic Perspectives](https://medichelpline.com/clinical-feed/frontiers-in-immunology-14-micrornas-in-immune-related-diseases-mechanism-functions-and-therapeutic.md)
- [Hyperuricemia and Gout in People Living with HIV: Systematic Review and Meta-analysis Protocol](https://medichelpline.com/clinical-feed/plos-one-6-urate-dysregulation-hyperuricemia-and-gout-among-people-living-with-hiv-a.md)

## Navigation
- [← Back to Infectious Disease Feed](https://medichelpline.com/clinical-feed/infectious-disease.md)
- [← All Clinical Specialties](https://medichelpline.com/clinical-feed.md)
## Medical & Regulatory Disclaimer

> [!CAUTION]
> MedicHelpline content is structured for research, educational, and professional discovery purposes. It does not constitute individual medical advice, clinical diagnosis, or treatment recommendations.
> Always verify dosing, contraindications, and regulatory alerts against official product labeling and primary regulatory sources before clinical decision-making.