Multidimensional Analysis of Innate Immune Suppression and Identification of Key Genes in Lymphedema

doi:10.3870/j.issn.1672-0741.26.03.031

Abstract

Abstract: Objective To investigate the role of innate immune responses in acute lymphedema and their association with susceptibility to infection through a multidimensional approach integrating bioinformatics,clinical validation, and animal experiments. Methods The mouse acute lymphedema dataset GSE4333 was downloaded from the Gene Expression Omnibus （GEO）. Differentially expressed genes （DEGs） were identified using limma （|log₂FC|>1, P_adj<0.05）,and gene set enrichment analysis （GSEA） was performed with GO, KEGG, and Hallmark gene sets via clusterProfiler.Peripheral blood was collected from patients with lower-extremity lymphedema （experimental group, n=5） and healthy controls （n=5） at Traditional Chinese and Western Medicine Hospital of Wuhan （Wuhan First Hospital）（June-July 2025）.Serum levels of S100A8, S100A9, NT5E, IRF7, IFITM1, and CORO1A were measured by ELISA. A mouse tail lymphedema model was established （n=6）, and tail tissues were harvested on postoperative day 10 for qPCR analysis of the 6 target genes; LYVE-1 immunofluorescence was used to assess lymphangiogenesis. Results A total of 151 DEGs （58 upregulated,93 downregulated） were identified. GSEA revealed significant negative enrichment of the innate immune response,the regulation of inflammatory response,the chemokine signaling pathway,and the oxidative phosphorylation pathway in acute lymphedema. Clinical validation demonstrated that serum levels of S100A8,S100A9,NT5E,IRF7,IFITM1, and CORO1A were significantly lower in lymphedema patients than in healthy controls （all P<0.01）. Animal experiments confirmed that the mRNA expression levels of S100a8, S100a9, Nt5e, Irf7, Ifitm1, and Coro1a in mouse lymphedematous tail tissues were significantly downregulated （all P<0.01）. Conclusion Acute lymphedema profoundly suppresses innate immune-related signaling pathways. The systemic downregulation of key immune regulators including S100A8, S100A9, NT5E, IRF7, IFITM1, and CORO1A may represent a critical molecular basis for increased susceptibility to infection in lymphedema patients. These molecules may serve as potential biomarkers for assessing immune function and as candidate targets for immunomodulatory therapy.

Key words: lymphedema, differentially expressed genes, gene set enrichment analysis（GSEA）, immune regulation, bioinformatics

CLC Number:

R654

Chen Feiyu, Xiong Wei, Chen Xi et al. Multidimensional Analysis of Innate Immune Suppression and Identification of Key Genes in Lymphedema[J]. Acta Medicinae Universitatis Scientiae et Technologiae Huazhong, 2026, 55(5): 607-613.

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