Abstract
72907 Spatial proteomics reveals unique immune inhibitory receptor expression in interface dermatoses
Journal of the American Academy of Dermatology, Vol.95(1 Suppl), p.AB410
07/2026
DOI: 10.1016/j.jaad.2026.04.1631
Abstract
Interface dermatitis, defined by basal keratinocyte damage and lymphocytic infiltrates, is a hallmark of some inflammatory skin diseases such as discoid lupus erythematosus (DLE) and lichen planus (LP). Despite overlapping histology, their immune regulatory mechanisms remain unclear. Using spatial proteomics, we aimed to define and compare immune inhibitory receptor expression in DLE and LP to identify shared and disease-specific mechanisms. We performed spatial proteomic analysis using the NanoString GeoMx Digital Spatial Profiler Immuno-Oncology panel (71 proteins) on formalin-fixed, paraffine-embedded archival skin biopsies from patients with DLE (n=10) and LP (n=10). Regions of interest were segmented into PanCK+ keratinocyte, CD4+, and CD8+ T-cells. Selected markers were validated by immunohistochemistry. Spatial proteomics revealed distinct clustering patterns. In DLE, CD4 + T-cells showed upregulation of VISTA, PD-L1, and ICOS, while CD8+ T-cells expressed PD-1 and CD27. In LP, T-cell compartments expressed TIM-3, CD25 and CD44, indicating broader activation. In PanCK+ keratinocytes, DLE samples upregulated fibronectin and phosphor-p38 MAPK, whereas LP samples increased ERK1/2 expression. VISTA was upregulated in both diseases across T-cell compartments. Several signaling pathways and immune checkpoints represent promising therapeutic targets for DLE, LP, or both. VISTA is a shared immune checkpoint with roles in cellular homeostasis and inflammation, making it a candidate for immune checkpoint agonist therapy. Likewise, CTLA-4 and ICOS warrant investigation given their co-expression in DLE and LP. In DLE, 4-1BB and PD-1 highlight the importance of memory T-cell activity, while the ERK1/2 pathway and EGFR may be targets in LP due to their involvement in keratinocyte-driven pathology.
Details
- Title: Subtitle
- 72907 Spatial proteomics reveals unique immune inhibitory receptor expression in interface dermatoses
- Creators
- Rachel Breidbart - Yale UniversityÜmmügülsüm Yıldız-Altay - Yale UniversityMichal Kidacki - Yale UniversityAnjali Jaiswal - Yale UniversityChristina Cho - Yale UniversityLieping Chen - Yale UniversityMatthew Vesely - Yale University
- Resource Type
- Abstract
- Publication Details
- Journal of the American Academy of Dermatology, Vol.95(1 Suppl), p.AB410
- DOI
- 10.1016/j.jaad.2026.04.1631
- ISSN
- 0190-9622
- Publisher
- Elsevier
- Language
- English
- Date published
- 07/2026
- Academic Unit
- Dermatology
- Record Identifier
- 9985182419302771
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