PMID- 34533976 OWN - NLM STAT- MEDLINE DCOM- 20220228 LR - 20220302 IS - 2470-9468 (Electronic) IS - 2470-9468 (Linking) VI - 6 IP - 63 DP - 2021 Sep 17 TI - Differential requirement for the Polycomb repressor complex 2 in dendritic cell and tissue-resident myeloid cell homeostasis. PG - eabf7268 LID - 10.1126/sciimmunol.abf7268 [doi] AB - Dendritic cells (DCs) and macrophages are at the forefront of immune responses, modifying their transcriptional programs in response to their tissue environment or immunological challenge. Posttranslational modifications of histones, such as histone H3 lysine-27 trimethylation (H3K27me3) by the Polycomb repressive complex 2 (PRC2), are tightly associated with epigenetic regulation of gene expression. To explore whether H3K27me3 is involved in either the establishment or function of the mononuclear phagocyte system, we selectively deleted core components of PRC2, either EZH2 or SUZ12, in CD11c-expressing myeloid cells. Unexpectedly, EZH2 deficiency neither prevented the deposition and maintenance of H3K27me3 in DCs nor hindered DC/macrophage homeostasis. In contrast, SUZ12 deficiency markedly impaired the capacity of DCs and macrophages to maintain H3K27me3. SUZ12 ablation induced a rapid loss of the alveolar macrophage and Langerhans cell networks under both steady state and inflammatory conditions because these cells could no longer proliferate to facilitate their self-renewal. Despite the reduced H3K27me3, DC development and function were unaffected by SUZ12 ablation, suggesting that PRC2-mediated gene repression was dispensable for DC homeostasis. Thus, the role of SUZ12 highlights the fundamentally different homeostatic mechanisms used by tissue-resident myeloid cells versus DCs. FAU - Zhan, Yifan AU - Zhan Y AUID- ORCID: 0000-0001-6974-0486 AD - Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia. AD - Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. AD - Drug Discovery, Shanghai Huaota Biopharma, Shanghai, China. FAU - Zhang, Yuxia AU - Zhang Y AUID- ORCID: 0000-0003-2715-0925 AD - Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia. AD - Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. AD - Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, Guangdong 510623, China. FAU - Zhang, Shengbo AU - Zhang S AUID- ORCID: 0000-0003-3870-0590 AD - Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia. AD - Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Coughlan, Hannah AU - Coughlan H AUID- ORCID: 0000-0002-2392-9942 AD - Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia. AD - Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Baldoni, Pedro L AU - Baldoni PL AUID- ORCID: 0000-0002-9510-8326 AD - Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia. AD - Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Jacquelot, Nicolas AU - Jacquelot N AUID- ORCID: 0000-0003-0282-1892 AD - Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia. AD - Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Cao, Wang H J AU - Cao WHJ AUID- ORCID: 0000-0001-8023-6096 AD - Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia. AD - Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Preston, Simon AU - Preston S AUID- ORCID: 0000-0001-8969-8297 AD - Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia. AD - Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Louis, Cynthia AU - Louis C AUID- ORCID: 0000-0001-8382-6358 AD - Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia. AD - Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Rautela, Jai AU - Rautela J AD - Biomedicine Discovery Institute, Monash University, Clayton, VIC 3800, Australia. FAU - Pellegrini, Marc AU - Pellegrini M AD - Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia. AD - Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Wicks, Ian P AU - Wicks IP AD - Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia. AD - Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Alexander, Warren S AU - Alexander WS AD - Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia. AD - Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Harrison, Leonard C AU - Harrison LC AUID- ORCID: 0000-0002-2500-8944 AD - Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia. AD - Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Lew, Andrew M AU - Lew AM AD - Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia. AD - Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. AD - Department of Microbiology and Immunology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Smyth, Gordon K AU - Smyth GK AUID- ORCID: 0000-0001-9221-2892 AD - Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia. AD - School of Mathematics and Statistics, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Nutt, Stephen L AU - Nutt SL AUID- ORCID: 0000-0002-0020-6637 AD - Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia. AD - Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. FAU - Chopin, Michael AU - Chopin M AUID- ORCID: 0000-0001-8812-2763 AD - Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, VIC 3052, Australia. AD - Department of Medical Biology, University of Melbourne, Parkville, VIC 3010, Australia. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210917 PL - United States TA - Sci Immunol JT - Science immunology JID - 101688624 RN - 0 (Suz12 protein, mouse) RN - EC 2.1.1.43 (Polycomb Repressive Complex 2) SB - IM MH - Animals MH - Dendritic Cells/*immunology MH - Homeostasis/*immunology MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Mice, Transgenic MH - Myeloid Cells/*immunology MH - Polycomb Repressive Complex 2/deficiency/*immunology EDAT- 2021/09/18 06:00 MHDA- 2022/03/01 06:00 CRDT- 2021/09/17 17:14 PHST- 2021/09/17 17:14 [entrez] PHST- 2021/09/18 06:00 [pubmed] PHST- 2022/03/01 06:00 [medline] AID - 10.1126/sciimmunol.abf7268 [doi] PST - ppublish SO - Sci Immunol. 2021 Sep 17;6(63):eabf7268. doi: 10.1126/sciimmunol.abf7268. Epub 2021 Sep 17.