Spatial transcriptomics reveals organized and distinct immune activation in cutaneous granulomatous disorders

IF 11.4 1区医学 Q1 ALLERGY

Journal of Allergy and Clinical Immunology Pub Date : 2024-11-01 DOI:10.1016/j.jaci.2024.07.021

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.

Abstract Image

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空间转录组学揭示了皮肤肉芽肿性疾病中有组织和独特的免疫激活。

背景：非感染性（炎症性）皮肤肉芽肿性疾病包括皮肤肉样瘤病（CS）、环状肉芽肿（GA）、类脂样坏死（NL）和坏死性黄疽瘤（NXG）。这些疾病在组织学上都是巨噬细胞占主导地位的炎症，但炎症结构和细胞外基质的改变模式各不相同。造成这些差异的潜在分子原因仍不清楚：了解这些疾病的空间基因表达特征：我们对 CS、GA、NL 和 NXG 病例进行了空间转录组学研究，以空间分辨的方式比较免疫激活模式和其他分子特征：CS的特征是极化的、空间有序的T辅助细胞（Th）1占主导地位的反应，同时伴有典型的巨噬细胞激活。GA的特征是Th1和Th2极化的混合模式，但在空间上是有组织的，同时伴有经典和替代性巨噬细胞活化。NL表现为Th1、Th2和Th17免疫同时激活，巨噬细胞激活模式混合。CS、GA 和 NL 都激活了 1 型免疫，包括 IL-32 的上调。NXG 表现出 CXCR4-CXCL12/14 趋化因子信号的上调和巨噬细胞的另类极化。细胞外基质的组织学改变与缺氧和糖酵解程序以及2型免疫激活相关：炎症性皮肤肉芽肿性疾病表现出独特的空间组织免疫激活，与标志性的组织学变化相关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Allergy and Clinical Immunology 医学-过敏

CiteScore

25.90

自引率

7.70%

发文量

1302

审稿时长

38 days

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.