Zbtb20 Restrains CD8 T Cell Immunometabolism and Restricts Memory Differentiation and Antitumor Immunity
CD8 T cell differentiation is orchestrated by dynamic metabolic changes that direct activation, proliferation, cytotoxic function, and epigenetic changes. We report that the BTB-ZF family transcriptional repressor Zbtb20 negatively regulates CD8 T cell metabolism and memory differentiation in mice....
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| Veröffentlicht in: | The Journal of immunology (1950) 2020-11, Vol.205 (10), p.2649-2666 |
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| container_title | The Journal of immunology (1950) |
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| creator | Sun, Yanbo Preiss, Nicholas K Valenteros, Kristine B Kamal, Yasmin Usherwood, Young-Kwang Frost, H Robert Usherwood, Edward J |
| description | CD8 T cell differentiation is orchestrated by dynamic metabolic changes that direct activation, proliferation, cytotoxic function, and epigenetic changes. We report that the BTB-ZF family transcriptional repressor Zbtb20 negatively regulates CD8 T cell metabolism and memory differentiation in mice. Effector and memory CD8 T cells with conditional Zbtb20 deficiency displayed enhanced mitochondrial and glycolytic metabolism, and memory CD8 T cells had enhanced spare respiratory capacity. Furthermore, Zbtb20-deficient CD8 T cells displayed increased flexibility in the use of mitochondrial fuel sources. Phenotypic and transcriptional skewing toward the memory fate was observed during the CD8 T cell response to
Memory cells mounted larger secondary responses and conferred better protection following tumor challenge. These data suggest that inactivation of Zbtb20 may offer an approach to enhance metabolic activity and flexibility and improve memory CD8 T cell differentiation, useful attributes for T cells used in adoptive immunotherapy. |
| doi_str_mv | 10.4049/jimmunol.2000459 |
| format | Article |
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Memory cells mounted larger secondary responses and conferred better protection following tumor challenge. These data suggest that inactivation of Zbtb20 may offer an approach to enhance metabolic activity and flexibility and improve memory CD8 T cell differentiation, useful attributes for T cells used in adoptive immunotherapy.</description><subject>Adoptive Transfer</subject><subject>Animals</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Differentiation - immunology</subject><subject>Disease Models, Animal</subject><subject>Energy Metabolism - genetics</subject><subject>Energy Metabolism - immunology</subject><subject>Gene Expression Regulation, Neoplastic - immunology</subject><subject>Glycolysis - genetics</subject><subject>Glycolysis - immunology</subject><subject>Humans</subject><subject>Immunologic Memory - genetics</subject><subject>Listeria monocytogenes - immunology</subject><subject>Listeriosis - immunology</subject><subject>Listeriosis - microbiology</subject><subject>Lymphocyte Activation</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mitochondria - metabolism</subject><subject>Neoplasms - genetics</subject><subject>Neoplasms - immunology</subject><subject>Neoplasms - pathology</subject><subject>Neoplasms - therapy</subject><subject>T-Lymphocytes, Cytotoxic - immunology</subject><subject>T-Lymphocytes, Cytotoxic - metabolism</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><issn>0022-1767</issn><issn>1550-6606</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9kMtOwzAQRS0EoqWwZ4X8AynjVxIvq5RCpSIkVDZsIjuxhas4qWJ30b8nNC2r0WjOvRodhB4JzDlw-bxz3h_arplTAOBCXqEpEQKSNIX0Gk0BKE1IlmYTdBfCbmBSoPwWTRiVMpe5mKKfbx01BfxpQuyVawMuljne4sI0DV6f2r2JSneNCx6rth5JV8WA343v-iNeOmtNb9roVHRde4IWwxYPw3nscPF4j26saoJ5OM8Z-lq9bIu3ZPPxui4Wm6RinMSE6ZrYinNhMpFpKq3KtNLAucrE8LtQPM_rWqRU5spwpSxTJKfAhOGV5imwGYKxt-q7EHpjy33vvOqPJYHyT1p5kVaepQ2RpzGyP2hv6v_AxRL7BZvRa04</recordid><startdate>20201115</startdate><enddate>20201115</enddate><creator>Sun, Yanbo</creator><creator>Preiss, Nicholas K</creator><creator>Valenteros, Kristine B</creator><creator>Kamal, Yasmin</creator><creator>Usherwood, Young-Kwang</creator><creator>Frost, H Robert</creator><creator>Usherwood, Edward J</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><orcidid>https://orcid.org/0000-0002-6794-9945</orcidid><orcidid>https://orcid.org/0000-0002-5611-9700</orcidid><orcidid>https://orcid.org/0000-0003-4423-7280</orcidid><orcidid>https://orcid.org/0000-0003-0463-0950</orcidid><orcidid>https://orcid.org/0000-0002-6731-7542</orcidid><orcidid>https://orcid.org/0000-0002-3294-8053</orcidid></search><sort><creationdate>20201115</creationdate><title>Zbtb20 Restrains CD8 T Cell Immunometabolism and Restricts Memory Differentiation and Antitumor Immunity</title><author>Sun, Yanbo ; Preiss, Nicholas K ; Valenteros, Kristine B ; Kamal, Yasmin ; Usherwood, Young-Kwang ; Frost, H Robert ; Usherwood, Edward J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c341t-3bd1fc445e757b29fa7bab044a750245a488dd56298ae4aaf3a182035e4cb4603</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adoptive Transfer</topic><topic>Animals</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Differentiation - immunology</topic><topic>Disease Models, Animal</topic><topic>Energy Metabolism - genetics</topic><topic>Energy Metabolism - immunology</topic><topic>Gene Expression Regulation, Neoplastic - immunology</topic><topic>Glycolysis - genetics</topic><topic>Glycolysis - immunology</topic><topic>Humans</topic><topic>Immunologic Memory - genetics</topic><topic>Listeria monocytogenes - immunology</topic><topic>Listeriosis - immunology</topic><topic>Listeriosis - microbiology</topic><topic>Lymphocyte Activation</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Mitochondria - metabolism</topic><topic>Neoplasms - genetics</topic><topic>Neoplasms - immunology</topic><topic>Neoplasms - pathology</topic><topic>Neoplasms - therapy</topic><topic>T-Lymphocytes, Cytotoxic - immunology</topic><topic>T-Lymphocytes, Cytotoxic - metabolism</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sun, Yanbo</creatorcontrib><creatorcontrib>Preiss, Nicholas K</creatorcontrib><creatorcontrib>Valenteros, Kristine B</creatorcontrib><creatorcontrib>Kamal, Yasmin</creatorcontrib><creatorcontrib>Usherwood, Young-Kwang</creatorcontrib><creatorcontrib>Frost, H Robert</creatorcontrib><creatorcontrib>Usherwood, Edward J</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><jtitle>The Journal of immunology (1950)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sun, Yanbo</au><au>Preiss, Nicholas K</au><au>Valenteros, Kristine B</au><au>Kamal, Yasmin</au><au>Usherwood, Young-Kwang</au><au>Frost, H Robert</au><au>Usherwood, Edward J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Zbtb20 Restrains CD8 T Cell Immunometabolism and Restricts Memory Differentiation and Antitumor Immunity</atitle><jtitle>The Journal of immunology (1950)</jtitle><addtitle>J Immunol</addtitle><date>2020-11-15</date><risdate>2020</risdate><volume>205</volume><issue>10</issue><spage>2649</spage><epage>2666</epage><pages>2649-2666</pages><issn>0022-1767</issn><eissn>1550-6606</eissn><abstract>CD8 T cell differentiation is orchestrated by dynamic metabolic changes that direct activation, proliferation, cytotoxic function, and epigenetic changes. We report that the BTB-ZF family transcriptional repressor Zbtb20 negatively regulates CD8 T cell metabolism and memory differentiation in mice. Effector and memory CD8 T cells with conditional Zbtb20 deficiency displayed enhanced mitochondrial and glycolytic metabolism, and memory CD8 T cells had enhanced spare respiratory capacity. Furthermore, Zbtb20-deficient CD8 T cells displayed increased flexibility in the use of mitochondrial fuel sources. Phenotypic and transcriptional skewing toward the memory fate was observed during the CD8 T cell response to
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| subjects | Adoptive Transfer Animals Cell Differentiation - genetics Cell Differentiation - immunology Disease Models, Animal Energy Metabolism - genetics Energy Metabolism - immunology Gene Expression Regulation, Neoplastic - immunology Glycolysis - genetics Glycolysis - immunology Humans Immunologic Memory - genetics Listeria monocytogenes - immunology Listeriosis - immunology Listeriosis - microbiology Lymphocyte Activation Mice Mice, Knockout Mitochondria - metabolism Neoplasms - genetics Neoplasms - immunology Neoplasms - pathology Neoplasms - therapy T-Lymphocytes, Cytotoxic - immunology T-Lymphocytes, Cytotoxic - metabolism Transcription Factors - genetics Transcription Factors - metabolism |
| title | Zbtb20 Restrains CD8 T Cell Immunometabolism and Restricts Memory Differentiation and Antitumor Immunity |
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