Identification and validation of immune related core transcription factors in NAFLD.

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide that endangers human health. Transcription factors (TFs) have gradually become hot spots for drug development in NAFLD for their impacts on metabolism. However, the specific TFs that regulate immune response in the development of NAFLD is not clear. This study aimed to investigate the TFs involved in the immune response of NAFLD and provide novel targets for drug development.

Methods: Microarray data were obtained from liver samples from 26 normal volunteers and 109 NAFLD patients using the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed by limma package. Differentially expressed transcription factors (DETFs) were obtained on DEGs combined with Cistrome Cancer database. Immune signatures and pathways hallmark were identified by ssGSSEA and GSVA. The co-regulation network was constructed by the above results. Further, quantitative Real-time Polymerase Chain Reaction (qRT-PCR), Western blot (WB) and Immunohistochemistry (IHC) were used to validate the relationship between and NAFLD. CIBERSORT analysis was performed to identify cell types to explore the relationship between differential expression of and immune cell surface markers.

Results: A total of 617 DEGs and six DETFs (, , , , , ) were obtained by differential analysis. Immune signatures and pathway hallmarks were identified by ssGSSEA and GSVA. and were screened through the co-regulatory networks of DEGs, DETFs, immune signatures and pathway hallmarks. Furthermore, qRT-PCR, WB and IHC indicated that but not was significantly upregulated in NAFLD. Finally, , our data confirmed that GTF2I has a wide impact on the immune profile by negatively regulating the expression of the chemokine receptor family (227/261, count of significance).

Conclusion: plays a role in NAFLD by negatively regulating the chemokine receptor family, which affects the immune profile. This study may provide a potential target for the diagnosis or therapy of NAFLD.