Computational IHC-H&E mapping in mouse models of colitis (H&E WSIs from paired H&E-IHC WSIs)

Inflammatory Bowel Disease (IBD) is characterized by chronic, dysregulated inflammation in the gastrointestinal tract. The heterogeneity of IBD is reflected through two major subtypes, Crohn’s Disease (CD) and Ulcerative Colitis (UC). CD and UC differ across symptomatic presentation, histology, immune responses, and treatment. While colitis mouse models have been influential in deciphering IBD pathogenesis, no single model captures the full heterogeneity of clinical disease. The translational capacity of mouse models may be augmented by shifting to multi-mouse model studies that aggregate analysis across various well-controlled phenotypes. Here, we evaluate the value of histology in multi-mouse model characterizations by building upon a previous pipeline that detects histological disease classes in hematoxylin and eosin (H&E)-stained murine colons. Specifically, we map immune marker positivity across serially-sectioned slides to H&E histological classes across the dextran sodium sulfate (DSS) chemical induction model and the intestinal epithelium-specific, inducible Villin-CreERT2;Klf5fl/fl (Klf5ΔIND) genetic model. In this study, we construct the beginning frameworks to define H&E-patch-based immunophenotypes based on IHC-H&E mappings.

炎症性肠病（Inflammatory Bowel Disease，IBD）以胃肠道慢性、失调性炎症为核心特征。IBD的异质性主要通过两大亚型体现，即克罗恩病（Crohn’s Disease，CD）与溃疡性结肠炎（Ulcerative Colitis，UC）。二者在临床表现、组织病理学特征、免疫应答模式及治疗方案上均存在显著差异。尽管结肠炎小鼠模型在解析IBD发病机制方面发挥了重要作用，但尚无单一模型能够完全复现临床疾病的全部异质性。若转向多小鼠模型研究，整合多种严格控制表型的分析结果，可有效提升小鼠模型的转化应用价值。本研究基于既往开发的、可识别苏木精-伊红（H&E）染色小鼠结肠组织病理学疾病类别的分析流程，评估组织病理学在多小鼠模型表征中的应用价值。具体而言，本研究将连续切片标本中的免疫标记物阳性表达情况，与葡聚糖硫酸钠（DSS）化学诱导模型及肠上皮特异性诱导型Villin-CreERT2；Klf5fl/fl（Klf5ΔIND）基因模型中的H&E组织病理学分类进行映射关联。本研究构建了基于免疫组化（Immunohistochemistry，IHC）-苏木精-伊红（H&E）映射关系、定义基于H&E切片斑块的免疫表型的初步研究框架。