Loss of MHC II ubiquitination inhibits the activation and differentiation of CD4 T cells
Loss of MHC class II ubiquitination in DCs downregulates integrin β2 and inhibits T-cell activation Peptide–MHC class II complexes (pMHC II) are degraded by MARCH-I-mediated ubiquitination, and the stabilization of pMHC II by loss of its ubiquitination is one phenotype defining the activation of con...
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| Veröffentlicht in: | International immunology 2014-05, Vol.26 (5), p.283-289 |
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| creator | Ishikawa, Rikiya Kajikawa, Mizuho Ishido, Satoshi |
| description | Loss of MHC class II ubiquitination in DCs downregulates integrin β2 and inhibits T-cell activation
Peptide–MHC class II complexes (pMHC II) are degraded by MARCH-I-mediated ubiquitination, and the stabilization of pMHC II by loss of its ubiquitination is one phenotype defining the activation of conventional dendritic cells (cDCs). However, the role of such stabilization of pMHC II in the context of T-cell activation/differentiation remains unclear. Here, we show that loss of pMHC II ubiquitination inhibits the activation and differentiation of CD4 T cells, probably through down-regulation of CD18/integrin β2 and their diminished IL-12 production in a cell intrinsic manner. The cDCs generated from mice whose pMHC II ubiquitination is inhibited had a decreased ability to activate naive CD4 T cells and induce Th1/Th17 differentiation. In addition, cDCs whose MHC II ubiquitination was inhibited showed down-regulation of CD18/integrin beta 2 and of IL-12 production. This unexpected finding suggests that loss of MHC II ubiquitination contributes to the negative feedback of CD4 T-cell immune responses. |
| doi_str_mv | 10.1093/intimm/dxt066 |
| format | Article |
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Peptide–MHC class II complexes (pMHC II) are degraded by MARCH-I-mediated ubiquitination, and the stabilization of pMHC II by loss of its ubiquitination is one phenotype defining the activation of conventional dendritic cells (cDCs). However, the role of such stabilization of pMHC II in the context of T-cell activation/differentiation remains unclear. Here, we show that loss of pMHC II ubiquitination inhibits the activation and differentiation of CD4 T cells, probably through down-regulation of CD18/integrin β2 and their diminished IL-12 production in a cell intrinsic manner. The cDCs generated from mice whose pMHC II ubiquitination is inhibited had a decreased ability to activate naive CD4 T cells and induce Th1/Th17 differentiation. In addition, cDCs whose MHC II ubiquitination was inhibited showed down-regulation of CD18/integrin beta 2 and of IL-12 production. This unexpected finding suggests that loss of MHC II ubiquitination contributes to the negative feedback of CD4 T-cell immune responses.</description><identifier>ISSN: 0953-8178</identifier><identifier>EISSN: 1460-2377</identifier><identifier>DOI: 10.1093/intimm/dxt066</identifier><identifier>PMID: 24370470</identifier><language>eng</language><publisher>UK: Oxford University Press</publisher><subject>Animals ; Antigen Presentation - genetics ; Antigen Presentation - immunology ; B7-2 Antigen - genetics ; B7-2 Antigen - immunology ; B7-2 Antigen - metabolism ; CD18 Antigens - immunology ; CD18 Antigens - metabolism ; CD4-Positive T-Lymphocytes - immunology ; CD4-Positive T-Lymphocytes - metabolism ; Cell Differentiation - genetics ; Cell Differentiation - immunology ; Cells, Cultured ; Coculture Techniques ; Dendritic Cells - immunology ; Dendritic Cells - metabolism ; Down-Regulation - immunology ; Flow Cytometry ; Histocompatibility Antigens Class II - genetics ; Histocompatibility Antigens Class II - immunology ; Histocompatibility Antigens Class II - metabolism ; Interleukin-12 - immunology ; Interleukin-12 - metabolism ; Lymphocyte Activation - genetics ; Lymphocyte Activation - immunology ; Mice, Knockout ; Mice, Transgenic ; Ubiquitin-Protein Ligases - genetics ; Ubiquitin-Protein Ligases - immunology ; Ubiquitin-Protein Ligases - metabolism ; Ubiquitination - genetics ; Ubiquitination - immunology</subject><ispartof>International immunology, 2014-05, Vol.26 (5), p.283-289</ispartof><rights>The Japanese Society for Immunology. 2013. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com 2013</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c350t-2792afd7ee7cedb9e3e67dfc3ee236725edb176d95f2b68fef08454ebb612d6c3</citedby><cites>FETCH-LOGICAL-c350t-2792afd7ee7cedb9e3e67dfc3ee236725edb176d95f2b68fef08454ebb612d6c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,778,782,1581,27907,27908</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24370470$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ishikawa, Rikiya</creatorcontrib><creatorcontrib>Kajikawa, Mizuho</creatorcontrib><creatorcontrib>Ishido, Satoshi</creatorcontrib><title>Loss of MHC II ubiquitination inhibits the activation and differentiation of CD4 T cells</title><title>International immunology</title><addtitle>INTIMM</addtitle><addtitle>Int Immunol</addtitle><description>Loss of MHC class II ubiquitination in DCs downregulates integrin β2 and inhibits T-cell activation
Peptide–MHC class II complexes (pMHC II) are degraded by MARCH-I-mediated ubiquitination, and the stabilization of pMHC II by loss of its ubiquitination is one phenotype defining the activation of conventional dendritic cells (cDCs). However, the role of such stabilization of pMHC II in the context of T-cell activation/differentiation remains unclear. Here, we show that loss of pMHC II ubiquitination inhibits the activation and differentiation of CD4 T cells, probably through down-regulation of CD18/integrin β2 and their diminished IL-12 production in a cell intrinsic manner. The cDCs generated from mice whose pMHC II ubiquitination is inhibited had a decreased ability to activate naive CD4 T cells and induce Th1/Th17 differentiation. In addition, cDCs whose MHC II ubiquitination was inhibited showed down-regulation of CD18/integrin beta 2 and of IL-12 production. This unexpected finding suggests that loss of MHC II ubiquitination contributes to the negative feedback of CD4 T-cell immune responses.</description><subject>Animals</subject><subject>Antigen Presentation - genetics</subject><subject>Antigen Presentation - immunology</subject><subject>B7-2 Antigen - genetics</subject><subject>B7-2 Antigen - immunology</subject><subject>B7-2 Antigen - metabolism</subject><subject>CD18 Antigens - immunology</subject><subject>CD18 Antigens - metabolism</subject><subject>CD4-Positive T-Lymphocytes - immunology</subject><subject>CD4-Positive T-Lymphocytes - metabolism</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Differentiation - immunology</subject><subject>Cells, Cultured</subject><subject>Coculture Techniques</subject><subject>Dendritic Cells - immunology</subject><subject>Dendritic Cells - metabolism</subject><subject>Down-Regulation - immunology</subject><subject>Flow Cytometry</subject><subject>Histocompatibility Antigens Class II - genetics</subject><subject>Histocompatibility Antigens Class II - immunology</subject><subject>Histocompatibility Antigens Class II - metabolism</subject><subject>Interleukin-12 - immunology</subject><subject>Interleukin-12 - metabolism</subject><subject>Lymphocyte Activation - genetics</subject><subject>Lymphocyte Activation - immunology</subject><subject>Mice, Knockout</subject><subject>Mice, Transgenic</subject><subject>Ubiquitin-Protein Ligases - genetics</subject><subject>Ubiquitin-Protein Ligases - immunology</subject><subject>Ubiquitin-Protein Ligases - metabolism</subject><subject>Ubiquitination - genetics</subject><subject>Ubiquitination - immunology</subject><issn>0953-8178</issn><issn>1460-2377</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkDtPwzAURi0EoqUwsiKPLKF-JHYyovBopSKWIrFFflyrRk1SYgfBvydVCoxMV_r06dx7D0KXlNxQUvC5b6Kv67n9jESIIzSlqSAJ41IeoykpMp7kVOYTdBbCGyGEs4KfoglLuSSpJFP0umpDwK3DT4sSL5e41_6999E3Kvq2wb7ZeO1jwHEDWJnoP8ZcNRZb7xx0MOwfswFS3qV4jQ1st-EcnTi1DXBxmDP08nC_LhfJ6vlxWd6uEsMzEhMmC6aclQDSgNUFcBDSOsMBGBeSZUNIpbBF5pgWuQNH8jRLQWtBmRWGz9D1yN117XsPIVa1D_sLVANtHyqaMUIpzUUxVJOxarrh6Q5ctet8rbqvipJqL7MaZVajzKF_dUD3ugb72_6x97e77Xf_sL4BPZCAqw</recordid><startdate>20140501</startdate><enddate>20140501</enddate><creator>Ishikawa, Rikiya</creator><creator>Kajikawa, Mizuho</creator><creator>Ishido, Satoshi</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20140501</creationdate><title>Loss of MHC II ubiquitination inhibits the activation and differentiation of CD4 T cells</title><author>Ishikawa, Rikiya ; Kajikawa, Mizuho ; Ishido, Satoshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c350t-2792afd7ee7cedb9e3e67dfc3ee236725edb176d95f2b68fef08454ebb612d6c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Antigen Presentation - genetics</topic><topic>Antigen Presentation - immunology</topic><topic>B7-2 Antigen - genetics</topic><topic>B7-2 Antigen - immunology</topic><topic>B7-2 Antigen - metabolism</topic><topic>CD18 Antigens - immunology</topic><topic>CD18 Antigens - metabolism</topic><topic>CD4-Positive T-Lymphocytes - immunology</topic><topic>CD4-Positive T-Lymphocytes - metabolism</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Differentiation - immunology</topic><topic>Cells, Cultured</topic><topic>Coculture Techniques</topic><topic>Dendritic Cells - immunology</topic><topic>Dendritic Cells - metabolism</topic><topic>Down-Regulation - immunology</topic><topic>Flow Cytometry</topic><topic>Histocompatibility Antigens Class II - genetics</topic><topic>Histocompatibility Antigens Class II - immunology</topic><topic>Histocompatibility Antigens Class II - metabolism</topic><topic>Interleukin-12 - immunology</topic><topic>Interleukin-12 - metabolism</topic><topic>Lymphocyte Activation - genetics</topic><topic>Lymphocyte Activation - immunology</topic><topic>Mice, Knockout</topic><topic>Mice, Transgenic</topic><topic>Ubiquitin-Protein Ligases - genetics</topic><topic>Ubiquitin-Protein Ligases - immunology</topic><topic>Ubiquitin-Protein Ligases - metabolism</topic><topic>Ubiquitination - genetics</topic><topic>Ubiquitination - immunology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ishikawa, Rikiya</creatorcontrib><creatorcontrib>Kajikawa, Mizuho</creatorcontrib><creatorcontrib>Ishido, Satoshi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>International immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ishikawa, Rikiya</au><au>Kajikawa, Mizuho</au><au>Ishido, Satoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Loss of MHC II ubiquitination inhibits the activation and differentiation of CD4 T cells</atitle><jtitle>International immunology</jtitle><stitle>INTIMM</stitle><addtitle>Int Immunol</addtitle><date>2014-05-01</date><risdate>2014</risdate><volume>26</volume><issue>5</issue><spage>283</spage><epage>289</epage><pages>283-289</pages><issn>0953-8178</issn><eissn>1460-2377</eissn><abstract>Loss of MHC class II ubiquitination in DCs downregulates integrin β2 and inhibits T-cell activation
Peptide–MHC class II complexes (pMHC II) are degraded by MARCH-I-mediated ubiquitination, and the stabilization of pMHC II by loss of its ubiquitination is one phenotype defining the activation of conventional dendritic cells (cDCs). However, the role of such stabilization of pMHC II in the context of T-cell activation/differentiation remains unclear. Here, we show that loss of pMHC II ubiquitination inhibits the activation and differentiation of CD4 T cells, probably through down-regulation of CD18/integrin β2 and their diminished IL-12 production in a cell intrinsic manner. The cDCs generated from mice whose pMHC II ubiquitination is inhibited had a decreased ability to activate naive CD4 T cells and induce Th1/Th17 differentiation. In addition, cDCs whose MHC II ubiquitination was inhibited showed down-regulation of CD18/integrin beta 2 and of IL-12 production. This unexpected finding suggests that loss of MHC II ubiquitination contributes to the negative feedback of CD4 T-cell immune responses.</abstract><cop>UK</cop><pub>Oxford University Press</pub><pmid>24370470</pmid><doi>10.1093/intimm/dxt066</doi><tpages>7</tpages></addata></record> |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Animals Antigen Presentation - genetics Antigen Presentation - immunology B7-2 Antigen - genetics B7-2 Antigen - immunology B7-2 Antigen - metabolism CD18 Antigens - immunology CD18 Antigens - metabolism CD4-Positive T-Lymphocytes - immunology CD4-Positive T-Lymphocytes - metabolism Cell Differentiation - genetics Cell Differentiation - immunology Cells, Cultured Coculture Techniques Dendritic Cells - immunology Dendritic Cells - metabolism Down-Regulation - immunology Flow Cytometry Histocompatibility Antigens Class II - genetics Histocompatibility Antigens Class II - immunology Histocompatibility Antigens Class II - metabolism Interleukin-12 - immunology Interleukin-12 - metabolism Lymphocyte Activation - genetics Lymphocyte Activation - immunology Mice, Knockout Mice, Transgenic Ubiquitin-Protein Ligases - genetics Ubiquitin-Protein Ligases - immunology Ubiquitin-Protein Ligases - metabolism Ubiquitination - genetics Ubiquitination - immunology |
| title | Loss of MHC II ubiquitination inhibits the activation and differentiation of CD4 T cells |
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