IκB Kinase ε Is an NFATc1 Kinase that Inhibits T Cell Immune Response
Activation of nuclear factor of activated T cells (NFAT) is crucial for immune responses. IKKε is an IκB kinase (IKK)-related kinase, and the function of IKKε remains obscure in T cells, despite its abundant expression. We report that IKKε inhibits NFAT activation and T cell responses by promoting N...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-07-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124716306969 |
| _version_ | 1811202820647419904 |
|---|---|
| author | Junjie Zhang Hao Feng Jun Zhao Emily R. Feldman Si-Yi Chen Weiming Yuan Canhua Huang Omid Akbari Scott A. Tibbetts Pinghui Feng |
| author_facet | Junjie Zhang Hao Feng Jun Zhao Emily R. Feldman Si-Yi Chen Weiming Yuan Canhua Huang Omid Akbari Scott A. Tibbetts Pinghui Feng |
| author_sort | Junjie Zhang |
| collection | DOAJ |
| description | Activation of nuclear factor of activated T cells (NFAT) is crucial for immune responses. IKKε is an IκB kinase (IKK)-related kinase, and the function of IKKε remains obscure in T cells, despite its abundant expression. We report that IKKε inhibits NFAT activation and T cell responses by promoting NFATc1 phosphorylation. During T cell activation, IKKε was transiently activated to phosphorylate NFATc1. Loss of IKKε elevated T cell antitumor and antiviral immunity and, therefore, reduced tumor development and persistent viral infection. IKKε was activated in CD8+ T cells of mice bearing melanoma or persistently infected with a model herpesvirus. These results collectively show that IKKε promotes NFATc1 phosphorylation and inhibits T cell responses, identifying IKKε as a crucial negative regulator of T cell activation and a potential target for immunotherapy. |
| first_indexed | 2024-04-12T02:45:03Z |
| format | Article |
| id | doaj.art-2586a015afbe4eafa2c830e94920837d |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-04-12T02:45:03Z |
| publishDate | 2016-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-2586a015afbe4eafa2c830e94920837d2022-12-22T03:51:11ZengElsevierCell Reports2211-12472016-07-0116240541810.1016/j.celrep.2016.05.083IκB Kinase ε Is an NFATc1 Kinase that Inhibits T Cell Immune ResponseJunjie Zhang0Hao Feng1Jun Zhao2Emily R. Feldman3Si-Yi Chen4Weiming Yuan5Canhua Huang6Omid Akbari7Scott A. Tibbetts8Pinghui Feng9Department of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USADepartment of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USADepartment of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USADepartment of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, 32610, USADepartment of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USADepartment of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USAState Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu, Sichuan 610041, P.R. ChinaDepartment of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USADepartment of Molecular Genetics and Microbiology, College of Medicine, University of Florida, Gainesville, FL, 32610, USADepartment of Molecular Microbiology and Immunology, Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Avenue, Los Angeles, CA 90033, USAActivation of nuclear factor of activated T cells (NFAT) is crucial for immune responses. IKKε is an IκB kinase (IKK)-related kinase, and the function of IKKε remains obscure in T cells, despite its abundant expression. We report that IKKε inhibits NFAT activation and T cell responses by promoting NFATc1 phosphorylation. During T cell activation, IKKε was transiently activated to phosphorylate NFATc1. Loss of IKKε elevated T cell antitumor and antiviral immunity and, therefore, reduced tumor development and persistent viral infection. IKKε was activated in CD8+ T cells of mice bearing melanoma or persistently infected with a model herpesvirus. These results collectively show that IKKε promotes NFATc1 phosphorylation and inhibits T cell responses, identifying IKKε as a crucial negative regulator of T cell activation and a potential target for immunotherapy.http://www.sciencedirect.com/science/article/pii/S2211124716306969 |
| spellingShingle | Junjie Zhang Hao Feng Jun Zhao Emily R. Feldman Si-Yi Chen Weiming Yuan Canhua Huang Omid Akbari Scott A. Tibbetts Pinghui Feng IκB Kinase ε Is an NFATc1 Kinase that Inhibits T Cell Immune Response Cell Reports |
| title | IκB Kinase ε Is an NFATc1 Kinase that Inhibits T Cell Immune Response |
| title_full | IκB Kinase ε Is an NFATc1 Kinase that Inhibits T Cell Immune Response |
| title_fullStr | IκB Kinase ε Is an NFATc1 Kinase that Inhibits T Cell Immune Response |
| title_full_unstemmed | IκB Kinase ε Is an NFATc1 Kinase that Inhibits T Cell Immune Response |
| title_short | IκB Kinase ε Is an NFATc1 Kinase that Inhibits T Cell Immune Response |
| title_sort | iκb kinase ε is an nfatc1 kinase that inhibits t cell immune response |
| url | http://www.sciencedirect.com/science/article/pii/S2211124716306969 |
| work_keys_str_mv | AT junjiezhang ikbkinaseeisannfatc1kinasethatinhibitstcellimmuneresponse AT haofeng ikbkinaseeisannfatc1kinasethatinhibitstcellimmuneresponse AT junzhao ikbkinaseeisannfatc1kinasethatinhibitstcellimmuneresponse AT emilyrfeldman ikbkinaseeisannfatc1kinasethatinhibitstcellimmuneresponse AT siyichen ikbkinaseeisannfatc1kinasethatinhibitstcellimmuneresponse AT weimingyuan ikbkinaseeisannfatc1kinasethatinhibitstcellimmuneresponse AT canhuahuang ikbkinaseeisannfatc1kinasethatinhibitstcellimmuneresponse AT omidakbari ikbkinaseeisannfatc1kinasethatinhibitstcellimmuneresponse AT scottatibbetts ikbkinaseeisannfatc1kinasethatinhibitstcellimmuneresponse AT pinghuifeng ikbkinaseeisannfatc1kinasethatinhibitstcellimmuneresponse |