PMID- 36172384 OWN - NLM STAT- MEDLINE DCOM- 20220930 LR - 20221103 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 13 DP - 2022 TI - L36G is associated with cutaneous antiviral competence in psoriasis. PG - 971071 LID - 10.3389/fimmu.2022.971071 [doi] LID - 971071 AB - BACKGROUND: Psoriasis 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. METHODS: The 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. RESULTS: We 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. CONCLUSION: IL36G 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. CI - Copyright (c) 2022 Lu, Chen, Shi, Yang, Wang, Dong, Kuang and Li. FAU - Lu, You-Wang AU - Lu YW AD - Department of Dermatology and Venereology, First Affiliated Hospital of Kunming Medical University, Kunming, China. AD - Hubei Provincial Key Laboratory of Occurrence and Intervention of Kidney Diseases, Medical College, Hubei Polytechnic University, Huangshi, China. FAU - Chen, Yong-Jun AU - Chen YJ AD - Department of Dermatology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, China. FAU - Shi, Nian AU - Shi N AD - Department of Dermatology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, China. FAU - Yang, Lu-Hui AU - Yang LH AD - Department of Dermatology and Venereology, First Affiliated Hospital of Kunming Medical University, Kunming, China. FAU - Wang, Hong-Mei AU - Wang HM AD - Department of Dermatology and Venereology, First Affiliated Hospital of Kunming Medical University, Kunming, China. FAU - Dong, Rong-Jing AU - Dong RJ AD - Department of Dermatology and Venereology, First Affiliated Hospital of Kunming Medical University, Kunming, China. AD - Hubei Provincial Key Laboratory of Occurrence and Intervention of Kidney Diseases, Medical College, Hubei Polytechnic University, Huangshi, China. AD - Department of Dermatology, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, China. FAU - Kuang, Yi-Qun AU - Kuang YQ AD - NHC Key Laboratory of Drug Addiction Medicine, First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China. AD - Scientific Research Laboratory Center, First Affiliated Hospital of Kunming Medical University, Kunming, China. FAU - Li, Yu-Ye AU - Li YY AD - Department of Dermatology and Venereology, First Affiliated Hospital of Kunming Medical University, Kunming, China. LA - eng PT - Journal Article DEP - 20220912 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Antiviral Agents) RN - 0 (Cytokines) RN - 0 (IL36G protein, human) RN - 0 (Interleukin-1) RN - 0 (Interleukins) RN - YL5FZ2Y5U1 (Methotrexate) SB - IM EIN - Front Immunol. 2022 Oct 17;13:1043240. PMID: 36325341 MH - Antiviral Agents MH - Computational Biology MH - Cytokines/genetics MH - *Gene Expression Profiling MH - Humans MH - *Interleukin-1/genetics MH - Interleukins/genetics MH - Methotrexate MH - *Psoriasis/genetics PMC - PMC9510771 OTO - NOTNLM OT - IL36G OT - antiviral protein (AVP) OT - keratinocyte OT - psoriasis OT - treatment COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/09/30 06:00 MHDA- 2022/10/01 06:00 PMCR- 2022/01/01 CRDT- 2022/09/29 02:17 PHST- 2022/06/16 00:00 [received] PHST- 2022/08/22 00:00 [accepted] PHST- 2022/09/29 02:17 [entrez] PHST- 2022/09/30 06:00 [pubmed] PHST- 2022/10/01 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2022.971071 [doi] PST - epublish SO - Front Immunol. 2022 Sep 12;13:971071. doi: 10.3389/fimmu.2022.971071. eCollection 2022.