Intestinal mucosal immune infiltration and inflammatory microenvironment in ankylosing spondylitis complicated by Crohn's disease:insights from single-cell sequencing and microarray data analysis
LUO Xi-qing
GU Jie-ruo
Abstract：Objective To analyze the characteristics of immune cell infiltration and activation of inflammation-related signaling pathways in the intestinal mucosa and peripheral blood inflammatory microenvironment of patients with ankylosing spondylitis(AS)coexisting with Crohn's Disease(CD).Methods CIBERSORT deconvolution of immune cell infiltration and gene set enrichment analysis(GSEA)were performed on microarray data from AS patients with CD ob-tained from the Gene Expression Omnibus(GEO)database.This analysis explored the infiltration of inflammatory immune cells and the activation status of inflammatory-related signaling pathways.Additionally,single-cell sequencing data from the intestinal mucosa and peripheral blood of AS patients with CD were used to compare the proportions of T cell sub-groups and validate the activation status of inflammation-related signaling pathways.Results Using the CIBERSORT al-gorithm to calculate the percentage of different immune cell subtypes in the chip samples,it was found that the content of CD8+T lymphocytes in the intestinal mucosal tissue of AS patients increased gradually with the progression of the disease,from non-enteritis to subclinical enteritis,and then to enteritis.Single-cell subgroup extraction and scoring for the acti-vation of inflammation-related pathway gene sets in lymphocytes from the intestinal mucosa and peripheral blood revealed that CD8+T lymphocytes in the intestinal mucosa of AS with CD had significantly increased activity in the TNFA-SIG-NALING-VIA-NFKB,INTERFERON-GAMMA-RESPONSE,and INFLAMMATORY-RESPONSE pathways com-pared to AS alone,but IL17-SIGNALING-PATHWAY showed no significant activation.In peripheral blood,the path-way activities of TNFA-SIGNALING-VIA-NFKB,INTERFERON-GAMMA-RESPONSE,INFLAMMATORY-RE-SPONSE,and IL17-SIGNALING-PATHWAY in CD8+T lymphocytes were significantly higher in the AS with CD group compared to the AS group.Single-cell sequencing also revealed an increased proportion of CD8+T cells in the pe-ripheral blood of AS patients with CD.Conclusion In AS patients with CD,the inflammatory signaling pathways related to TNF-α and IFN-γ are significantly activated in the intestinal mucosa.The proportion of CD8+T lymphocytes in pe-ripheral blood is increased,serving as a potential indicator for determining the coexistence of AS and enteritis.
Keywords：ankylosing spondylitissingle cell sequencinginflammatory microenvironment
Publication Date：2024-01-28
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：13( 50-62 )