Identification of immune characteristic landscapes related to autophagy in ischemic stroke

Abstract

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Ischemic stroke (IS) is a common and grievous nervous system disease. Both autophagy activation and immune response after cerebral ischemia play important roles in the development of IS. Many studies have revealed a close interplay between autophagy and immunity. However, little is known about how autophagy influences the immune characteristics of IS. Hence, the study aims to systematically explore the role of autophagy and its impact on immune characteristics in IS. We first compared the expression differences of autophagy genes in a training set and identified 20 dysregulated autophagy genes between healthy and IS samples. An autophagy-related classifier composed of seven genes was further established and could well distinguish healthy and IS samples. Then, the association between autophagy and immune characteristics, including infiltrating immunocytes, activity of immune reactions, and HLA gene expression, was investigated. The results showed that autophagy closely correlated with immune characteristics, such as NAMPT and ARNT significantly related to infiltrating immunocytes; PPP1R15A and CASP3 significantly related to activity of immune reactions; and NAMPT and ATG16L2 significantly related to HLA genes. Next, two distinct autophagy expression patterns were identified by unsupervised clustering analysis, and diverse immune characteristics were discovered between them. A total of 5481 autophagy phenotype-related genes were obtained between two expression patterns, and their biological functions revealed that these genes were involved in immune-related biological pathways. Finally, five dysregulated autophagy genes (FOS, MAP1LC3B, ERO1L, ARNT, and PPP1R15A) were proved between IS and healthy samples using another two validation sets. Our results illustrated that autophagy had a dramatic effect on the immunity of IS and provided a novel sight into understanding the pathogenesis of IS.

Keywords

• autophagy
• immune characteristic
• ischemic stroke
• correlation analysis
• weighted gene co-expression network analysis (WGCNA)