Joseph Daccache BA , Eunsuh Park , Muhammad Junejo MD , Mariam Abdelghaffar BS , Erica Hwang BS , Chitrasen Mohanty MS , Chandra K. Singh PhD , Guilin Wang PhD , John O. Wheeler MS , Bridget E. Shields MD , Caroline A. Nelson MD , Yiwei Wang PhD , William Damsky MD, PhD
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引用次数: 0
Abstract
Background
Noninfectious (inflammatory) cutaneous granulomatous disorders include cutaneous sarcoidosis (CS), granuloma annulare (GA), necrobiosis lipoidica (NL), and necrobiotic xanthogranuloma (NXG). These disorders share macrophage-predominant inflammation histologically, but the inflammatory architecture and the pattern of extracellular matrix alteration varies. The underlying molecular explanations for these differences remain unclear.
Objective
We sought to understand spatial gene expression characteristics in these disorders.
Methods
We performed spatial transcriptomics in cases of CS, GA, NL, and NXG to compare patterns of immune activation and other molecular features in a spatially resolved fashion.
Results
CS is characterized by a polarized, spatially organized type 1-predominant response with classical macrophage activation. GA is characterized by a mixed but spatially organized pattern of type 1 and type 2 polarization with both classical and alternative macrophage activation. NL showed concomitant activation of type 1, type 2, and type 3 immunity with a mixed pattern of macrophage activation. Activation of type 1 immunity was shared among, CS, GA, and NL and included upregulation of IL-32. NXG showed upregulation of CXCR4-CXCL12/14 chemokine signaling and exaggerated alternative macrophage polarization. Histologic alteration of extracellular matrix correlated with hypoxia and glycolysis programs and type 2 immune activation.
Conclusions
Inflammatory cutaneous granulomatous disorders show distinct and spatially organized immune activation that correlate with hallmark histologic changes.
期刊介绍：
The Journal of Allergy and Clinical Immunology is a prestigious publication that features groundbreaking research in the fields of Allergy, Asthma, and Immunology. This influential journal publishes high-impact research papers that explore various topics, including asthma, food allergy, allergic rhinitis, atopic dermatitis, primary immune deficiencies, occupational and environmental allergy, and other allergic and immunologic diseases. The articles not only report on clinical trials and mechanistic studies but also provide insights into novel therapies, underlying mechanisms, and important discoveries that contribute to our understanding of these diseases. By sharing this valuable information, the journal aims to enhance the diagnosis and management of patients in the future.
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