PMID- 36341359 OWN - NLM STAT- MEDLINE DCOM- 20221108 LR - 20221109 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 13 DP - 2022 TI - Transcriptomics and quantitative proteomics reveal changes after second stimulation of bone marrow-derived macrophages from lupus-prone MRL/lpr mice. PG - 1004232 LID - 10.3389/fimmu.2022.1004232 [doi] LID - 1004232 AB - Innate immune memory can cause the occurrence and exacerbation of autoimmune diseases, and it is as well as being strongly associated with the pathogenesis of systemic lupus erythematosus (SLE), however, the specific mechanism remains to be further studied. We learned that IFN-gamma stimulation generated innate immune memory in bone marrow-derived macrophages (BMDMs) and activated memory interferon-stimulated genes (ISGs). This research used IFN-gamma and lipopolysaccharide (LPS) to treat BMDMs with lupus-prone MRL/lpr mice and showed that particular memory ISGs were substantially elevated in prestimulated macrophages. In order to identify the differentially expressed genes (DEGs), researchers turned to RNA-seq. GO and KEGG analysis showed that up-regulated DEGs were enriched in defense and innate immune responses, and were related to the expression of pattern recognition receptors (PRRs)-related pathways in macrophages. TMT-based proteome analysis revealed differentially expressed proteins (DEPs) up-regulated in BMDMs were abundant in metabolic pathways such as glucose metabolism. Our study found that after the secondary stimulation of MRL/lpr mice, the expression of PRRs in innate immune cells was changed, and IFN-related pathways were activated to release a large number of ISGs to promote the secondary response. At the same time, related metabolic modes such as glycolysis were enhanced, and epigenetic changes may occur. Therefore, SLE is brought on, maintained, and worsened by a variety of factors that work together to produce innate immune memory. CI - Copyright (c) 2022 Chen, Wu, Wang, Li, Shen, Zhao, Ozato and Li. FAU - Chen, Keyue AU - Chen K AD - Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China. FAU - Wu, Tiyun AU - Wu T AD - Division of Developmental Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States. FAU - Wang, Danyan AU - Wang D AD - Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China. FAU - Li, Rong AU - Li R AD - Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China. FAU - Shen, Xiangfeng AU - Shen X AD - Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China. FAU - Zhao, Ting AU - Zhao T AD - Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China. FAU - Ozato, Keiko AU - Ozato K AD - Division of Developmental Biology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, United States. FAU - Li, Rongqun AU - Li R AD - Key Laboratory of Chinese Medicine Rheumatology of Zhejiang Province, School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China. LA - eng GR - ZIA HD001310/ImNIH/Intramural NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't DEP - 20221019 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 SB - IM MH - Mice MH - Animals MH - Mice, Inbred MRL lpr MH - *Transcriptome MH - Proteomics MH - *Lupus Erythematosus, Systemic MH - Macrophages/pathology PMC - PMC9627492 OTO - NOTNLM OT - MRL/lpr mice OT - RNA-seq OT - innate immune memory OT - proteome OT - systemic lupus erythematosus 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. The reviewer LL declared a shared parent affiliation with the authors KC, DW, RL, XS, TZ and RL to the handling editor at the time of review. EDAT- 2022/11/08 06:00 MHDA- 2022/11/09 06:00 PMCR- 2022/01/01 CRDT- 2022/11/07 05:17 PHST- 2022/07/27 00:00 [received] PHST- 2022/09/27 00:00 [accepted] PHST- 2022/11/07 05:17 [entrez] PHST- 2022/11/08 06:00 [pubmed] PHST- 2022/11/09 06:00 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2022.1004232 [doi] PST - epublish SO - Front Immunol. 2022 Oct 19;13:1004232. doi: 10.3389/fimmu.2022.1004232. eCollection 2022.