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Ubiquitination of pMHC-II by the E3 ubiquitin ligase March-I regulates surface expression and survival of pMHC-II in DCs. We now show that despite their high levels of surface pMHC-II, MHC class II (MHC-II) ubiquitination\u2013deficient mouse DCs are functionally defective; they are poor stimulators of naive CD4 T cells and secrete IL-12 in response to LPS stimulation poorly. MHC-II ubiquitination\u2013mutant DC defects are cell intrinsic, and single-cell RNA sequencing demonstrates that these DCs have an altered gene expression signature as compared with wild-type DCs. Curiously, these functional and gene transcription defects are reversed by activating the DCs with LPS. These results show that dysregulation of MHC-II turnover suppresses DC development and function.<\/jats:p>","DOI":"10.4049\/jimmunol.2000975","type":"journal-article","created":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T15:15:23Z","timestamp":1607958923000},"page":"494-504","source":"Crossref","is-referenced-by-count":18,"title":["Ubiquitination of MHC Class II by March-I Regulates Dendritic Cell Fitness"],"prefix":"10.1093","volume":"206","author":[{"given":"Hei Jung","family":"Kim","sequence":"first","affiliation":[{"name":"Experimental Immunology Branch, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4908-7384","authenticated-orcid":false,"given":"Joanna","family":"Bandola-Simon","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Ishido","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Hyogo College of Medicine , Nishinomiya 663-8501 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathan W","family":"Wong","sequence":"additional","affiliation":[{"name":"Center for Cancer Research Collaborative Bioinformatics Resource, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"},{"name":"Advanced Biomedical Computational Sciences, Frederick National Laboratory for Cancer Research , Frederick, MD 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishal N","family":"Koparde","sequence":"additional","affiliation":[{"name":"Center for Cancer Research Collaborative Bioinformatics Resource, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"},{"name":"Advanced Biomedical Computational Sciences, Frederick National Laboratory for Cancer Research , Frederick, MD 21702"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maggie","family":"Cam","sequence":"additional","affiliation":[{"name":"Center for Cancer Research Collaborative Bioinformatics Resource, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8949-9172","authenticated-orcid":false,"given":"Paul A","family":"Roche","sequence":"additional","affiliation":[{"name":"Experimental Immunology Branch, National Cancer Institute, National Institutes of Health , Bethesda, MD 20892"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,2,1]]},"reference":[{"key":"2025022610331464200_r1","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nri3818","article-title":"The ins and outs of MHC class II-mediated antigen processing and presentation","volume":"15","author":"Roche","year":"2015","journal-title":"Nat. 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