The 2025 Society of Investigative Dermatology (SID) Annual Meeting was held in San Diego, California, from Wednesday, May 7 to Saturday, May 10. Over 1,200 basic and clinical dermatology scientists attended over 50 sessions and 300 presentations. This report provides an overview of the key psoriasis sessions, including the IPC Symposium: Not the Usual Suspects – Lesser Known Cells in Psoriasis. Download the full 2025 SID Congress Report for complete details, or read on for session summaries.
IPC SYMPOSIUM: NOT THE USUAL SUSPECTS – LESSER KNOWN CELLS IN PSORIASIS
IPC Symposium summaries written by Rundong Jiang.
Overview of Psoriasis Pathogenesis
Johann Gudjonsson, MD, PhD, IPC Board Member
Dr. Johann Gudjonsson described psoriasis as a chronic, immune-mediated disease driven by keratinocyte hyperproliferation and perivascular lymphocytic infiltrates alongside T-cell IL-17A and neutrophil IL-36 pathways. He emphasized insights from over 160 genetic risk loci and emerging roles for melanocytes, neuroimmune interactions, activated endothelium, fibroblasts, and neutrophils in perpetuating the multicellular inflammatory network.
Neutrophils and Psoriasis
Francesca Capon, PhD, IPC Councilor
Dr. Francesca Capon demonstrated that neutrophils are central amplifiers of psoriasis inflammation, with IL36RN mutations in generalized pustular psoriasis driving protease-mediated IL-36 activation and neutrophil accumulation, and MPO mutations impairing apoptosis to sustain inflammatory loops. In plaque psoriasis, she noted neutrophils migrate from the dermis to epidermis under IL-8, IL-17, and IL-19 signals and form neutrophil extracellular traps (NETs) that activate keratinocytes, dendritic cells, and Th17 responses, cementing their role as key drivers of disease progression.
Fibroblasts and Psoriasis
Satveer Mahil, PhD, FRCP, IPC Councilor
Dr. Satveer Mahil presented single-cell RNA-seq data revealing that, in psoriatic lesions, IL-17A and TNF drive an expansion of pro-inflammatory myofibroblast-like fibroblasts, marked by WNT5A, IL-24, and CXCL8, that localize to the upper dermis and fuel keratinocyte proliferation and leukocyte infiltration. She further showed that IL-23 blockade rapidly reprograms these fibroblasts, highlighting their dynamic plasticity and central role in orchestrating chronic inflammation through both structural support and immune modulation.
Melanocytes and Psoriasis
Mehdi Rashighi, MD
Dr. Mehdi Rashighi explored how melanocytes, long viewed as passive bystanders, can express the autoantigen ADAMTSL5 in HLA-C*06:02⁺ individuals and present aberrant peptides (via ERAP1 variants) to CD8⁺ T cells, driving local Tc17 activation and cytokine release. He also noted that IL-17 and TNF synergistically suppress melanogenesis, linking pigmentary changes to an amplifying feedback loop between melanocytes and psoriatic inflammation.
Endothelial Cells and Psoriasis
Michael Garshick, MD, IPC Councilor
Dr. Michael Garshick demonstrated that psoriatic cytokines IL-17A, TNF-α, and IL-6 drive endothelial activation and dysfunction, corroborated by NF-κB pathway upregulation in vascular endothelium and platelet hyperactivation, and that IL-17/TNF blockade, alongside adjunctive low-dose aspirin and statin therapy, can attenuate vascular inflammation. He emphasized integrating cardiovascular risk management in psoriasis care to mitigate systemic atherogenesis and reduce myocardial infarction risk.
Nerve Cells and Psoriasis
Daniel Kaplan, MD, PhD
Dr. Daniel H. Kaplan showed that activation of TRPV1⁺ nociceptors alone triggers a Type 17 inflammatory cascade, upregulating IL-23, IL-6, IL-17, and IL-22, and that substance P-mediated mast cell degranulation drives dermal dendritic cell clustering for IL-23 production. He further demonstrated that sustained IL-23 expression requires repeated neuronal stimulation and that loss of Mrgprb2 abrogates this neuroimmune circuit, positioning peripheral neurons as active regulators of psoriasis pathogenesis.
ABSTRACT PRESENTATIONS
Abstract summaries provided by original presenters and published with their permission.
Regulation of IL-6 and Calcitonin Gene-related Peptide (CGRP) Expression by Vitamin (VD) in Transformed Dorsal Root Ganglion (DRG) Cells
Richard D. Granstein, MD
Dr. Richard D. Granstein demonstrated that both 25-hydroxyvitamin D₃ and its active form 1,25-dihydroxyvitamin D₃ dose-dependently suppress IL-6 secretion and CGRP production in differentiated DRG neurons, suggesting that vitamin D’s benefits in psoriasis may stem in part from modulating sensory nerve–driven inflammation
Neutrophils are Primed for Enhanced Inflammasome Activation in Skin Microvasculature During Adhesion via E-selectin
Yoshiaki Matsushima, MD, PhD
Dr. Yoshiaki Matsushima demonstrated that mechanical rolling of neutrophils on E-selectin rapidly doubles inflammasome (caspase-1) activity, further amplified by LPS, S100A8/A9, or TNFα, and that psoriatic neutrophils exhibit even higher baseline and stimulated priming. Blocking E-selectin–L-selectin interactions with GMI-1687 abrogates this effect, uncovering a novel, early vascular adhesion-driven mechanism fueling psoriatic inflammation.
OTHER PSORIASIS SESSIONS
Other Psoriasis Sessions summaries written by Huidi Shucheng, MD, PhD, MPH, 2024 IPC Fellow.
A Senescent Subpopulation of Fibroblasts Induce Inflammation in Psoriasis through APOE
Qiaochu Jiang, MD
Dr. Qiaochu Jiang identified a unique, senescent subpopulation of APOE-expressing fibroblasts enriched in psoriatic lesions that secrete SASP factors (IL-6, MMP3) and drive neutrophil migration via CXCL1/2 induction through a PGE₂/EP4/AKT/NF-κB axis. In IMQ mouse models, fibroblast-specific Apoe knockout or EP4 antagonism reduced epidermal thickening and IL-23/IL-17A levels. At the same time, the senolytic ABT-263 selectively cleared APOE⁺ cells to halve plaque area, highlighting APOE⁺ fibroblasts as a promising dual senescence-inflammation target.
Eugene Farber Lecture – Psoriasis: From Molecular Endotypes to Treatment Resistance
Michel Gilliet, MD, IPC Councilor
Dr. Michel Gilliet outlined a molecular endotyping framework, IFN-I (acute), Th17 (chronic plaque), and neutrophilic (pustular), and demonstrated that non-responders to IL-23/IL-17 inhibitors show IFN-I dominance driven by pDCs and low C1q levels. He proposed precision strategies including C1qBP agonists, pDC/IFN-I blockade, and epigenetic modifiers, backed by real-time transcriptomic profiling, to prevent endotype shifts and overcome treatment resistance.
IL-17 Inhibitors vs. Methotrexate in Preventing New-Onset Psoriatic Arthritis in Psoriasis Patients: A Retrospective Population-Level Analysis
Ryan Chan, MD
Dr. Ryan Chan reported that, in a propensity-matched cohort of 17,062 psoriasis patients from the TriNetX database, IL-17 inhibitors reduced 5-year PsA incidence by 15% versus methotrexate (6.1% vs. 7.2%; HR 1.214, p < 0.001), with a 47% greater risk reduction in HLA-B27⁺ patients. He linked these clinical benefits to IL-17i’s suppression of the synovio-entheseal IL-23/IL-17 axis, evidenced by 40% lower serum IL-23 and improved enthesitis scores, and suggested IL-17i as first-line therapy for high-risk individuals, while underscoring the need for prospective imaging studies.
IL-17D-Induced Metabolic Reprogramming Empowers Inflammatory Memory in Keratinocytes to Promote Psoriasis Relapse
Yuping Lai, PhD
Dr. Yuping Lai showed that IL-17D reprograms keratinocytes from oxidative phosphorylation to glycolysis, raising lactate levels that drive histone H3K18 lactylation and boost expression of psoriasis genes (DEFB4, S100A7). In IMQ models, IL-17D knockout cut relapse by 60%, while LDH inhibition reduced epidermal thickness by 45%, supporting strategies targeting lactate transport (MCT1 inhibitors) or IL-17D neutralization to disrupt metabolic–epigenetic loops and prevent disease recurrence.
AX-158 Proof-of-Mechanism Safety Study: Evaluating a Novel T Cell Receptor (TCR) Signal Modulator in Patients with Mild-to-Moderate Plaque Psoriasis
Christopher VanDeusen, PhD
Dr. Christopher VanDeusen reported that AX-158, a first-in-class oral TCR modulator targeting the Nck-SH3.1 domain, achieved a 34.6% greater mean PASI reduction versus placebo (p=0.03), with 57% of treated patients reaching ≥25% improvement by week 12, and lesional RNA-seq showing downregulation of IL17A, S100A7, and CCL20. He further demonstrated selective depletion of pathogenic CCR6⁺CD4⁺ T cells while sparing Tregs, a favorable safety profile with only mild AEs. He outlined an upcoming Phase III trial to assess PASI-75/90 responses and biomarker-driven patient selection.
Efficacy and Safety of Once-Daily Roflumilast Foam 0.3% for Psoriasis of the Scalp and Body Involving Knees/Elbows: Subgroup Results from the Phase 3 Arrector Trial
Saori Kato, PhD
Dr. Saori Kato reported that once-daily roflumilast foam 0.3% achieved a 43% B-IGA success rate at week 8 (clear/almost clear with ≥2-grade improvement) versus 18% for vehicle (p<0.001), with PASI-75/90 responses on knees (39%/31% vs. 10%/8%) and elbows (42%/30% vs. 19%/13%) all favoring ROF (p<0.001). Histology confirmed a 50% reduction in epidermal thickness and 60% fewer Ki-67⁺ keratinocytes. At the same time, safety was excellent, with only 6.2% mild site irritation and no steroid-associated atrophy, highlighting ROF’s foam formulation as a well-tolerated, first-line topical for recalcitrant, high-friction areas.
Unveiling the IL-36/IFNK Axis in Sex-Biased Generalized Pustular Psoriasis
Mrinal Sarkar, PhD
Dr. Mrinal Sarkar revealed that female keratinocytes exhibit 3.8-fold higher IFN-κ and 2.5-fold greater IL-36G expression, driven by epigenetic priming at IFN-κ promoters, and that IL-36G knockout cuts IL-17A secretion by 70%, pinpointing a sex-specific inflammatory loop. He further demonstrated a spatial circuit in GPP lesions where TNFSF15⁺ neutrophils and IL-36G⁺ keratinocytes amplify each other and showed that estrogen modulates this axis in vivo, supporting combined IL-36R and JAK inhibition as a precision therapy for female-predominant disease.
We encourage you to download the full 2025 SID Congress Report for detailed session summaries and in-depth coverage of findings.
