机构:[1]Department of Dermatology and Venereology, First Affiliated Hospital of Kunming Medical University, Kunming, China, 内科科室皮肤科昆明医科大学附属第一医院[2]Hubei Provincial Key Laboratory of Occurrence and Intervention of Kidney Diseases, Medical College, Hubei Polytechnic University, Huangshi, China, [3]Department of Dermatology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, China, [4]NHC Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China, 医技科室医学影像中心CT室昆明医科大学附属第一医院[5]Scientific Research Laboratory Center, First Affiliated Hospital of Kunming Medical University, Kunming, China昆明医科大学附属第一医院
BackgroundPsoriasis is a common inflammatory skin disease that has a great impact on patients' physical and mental health. However, the causes and underlying molecular mechanisms of psoriasis are still largely unknown. MethodsThe expression profiles of genes from psoriatic lesion samples and skin samples from healthy controls were integrated via the sva software package, and differentially expressed genes (DEGs) between psoriasis and healthy skin were screened by the limma package. Furthermore, GO and KEGG pathway enrichments for the DEGs were performed using the Clusterprofiler package. Protein-protein interaction (PPI) networks for the DEGs were then constructed to identify hub genes. scGESA analysis was performed on a single-cell RNA sequencing dataset via irGSEA. In order to find the cytokines correlated with the hub genes expression, single cell weighted gene co-expression network analyses (scWGCNA) were utilized to build a gene co-expression network. Furthermore, the featured genes of psoriasis found in suprabasal keratinocytes were intersected with hub genes. We then analyzed the expression of the intersection genes and cytokines in the integrated dataset. After that, we used other datasets to reveal the changes in the intersection genes' expression levels during biological therapy. The relationship between intersection genes and PASI scores was also explored. ResultsWe identified 148 DEGs between psoriatic and healthy samples. GO and KEGG pathway enrichment analysis suggested that DEGs are mainly involved in the defense response to other organisms. The PPI network showed that 11 antiviral proteins (AVPs) were hub genes. scGSEA analysis in the single-cell transcriptome dataset showed that those hub genes are highly expressed in keratinocytes, especially in suprabasal keratinocytes. ISG15, MX1, IFI44L, and IFI27 were the characteristic genes of psoriasis in suprabasal keratinocytes. scWGCNA showed that three cytokines-IL36G, MIF, and IL17RA-were co-expressed in the turquoise module. Only interleukin-36 gamma (IL36G) was positively correlated with AVPs in the integrated dataset. IL36G and AVPs were found co-expressed in a substantial number of suprabasal keratinocytes. Furthermore, we found that the expression levels of IL36G and the 4 AVPs showed positive correlation with PASI score in patients with psoriasis, and that these levels decreased significantly during treatment with biological therapies, but not with methotrexate. ConclusionIL36G and antiviral proteins may be closely related with the pathogenesis of psoriasis, and they may represent new candidate molecular markers for the occurrence and severity of psoriasis.
基金:
National Natural Science Foundation of China [81860553]; Talent Introduction Project of Hubei Polytechnic University [21xjz33R, 21xjz34R]; "Ten-thousand Talents Program" of Yunnan Province [YNWR-MY-2018-039]; Project of AIDS Bureau of Yunnan Province; Yunnan Province Clinical Center for Skin Immune Diseases [ZX2019-03-02]; Yunnan Province Clinical Research Center for Skin Immune Diseases [2019ZF012]
第一作者机构:[1]Department of Dermatology and Venereology, First Affiliated Hospital of Kunming Medical University, Kunming, China, [2]Hubei Provincial Key Laboratory of Occurrence and Intervention of Kidney Diseases, Medical College, Hubei Polytechnic University, Huangshi, China,
通讯作者:
通讯机构:[1]Department of Dermatology and Venereology, First Affiliated Hospital of Kunming Medical University, Kunming, China, [2]Hubei Provincial Key Laboratory of Occurrence and Intervention of Kidney Diseases, Medical College, Hubei Polytechnic University, Huangshi, China, [3]Department of Dermatology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, China, [4]NHC Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China, [5]Scientific Research Laboratory Center, First Affiliated Hospital of Kunming Medical University, Kunming, China
推荐引用方式(GB/T 7714):
lu you-wang,chen yong-jun,shi nian,et al.L36G is associated with cutaneous antiviral competence in psoriasis[J].FRONTIERS IN IMMUNOLOGY.2022,13:doi:10.3389/fimmu.2022.971071.
APA:
lu,you-wang,chen,yong-jun,shi,nian,yang,lu-hui,wang,hong-mei...&li,yu-ye.(2022).L36G is associated with cutaneous antiviral competence in psoriasis.FRONTIERS IN IMMUNOLOGY,13,
MLA:
lu,you-wang,et al."L36G is associated with cutaneous antiviral competence in psoriasis".FRONTIERS IN IMMUNOLOGY 13.(2022)