Cord Blood CD8+ T Cells Have a Natural Propensity to Express IL-4 in a Fatty Acid Metabolism and Caspase Activation-Dependent Manner
How T cells differentiate in the neonate may critically determine the ability of the infant to cope with infections, respond to vaccines and avert allergies. Previously, we found that naïve cord blood CD4+ T cells differentiated toward an IL-4-expressing phenotype when activated in the presence of T...
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-04-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00879/full |
| _version_ | 1828369453407010816 |
|---|---|
| author | Yuxia Zhang Yuxia Zhang Yuxia Zhang Jovana Maksimovic Jovana Maksimovic Bing Huang David Peter De Souza David Peter De Souza Gaetano Naselli Gaetano Naselli Huan Chen Li Zhang Kai Weng Hanquan Liang Yanhui Xu Yanhui Xu John M. Wentworth John M. Wentworth Nicholas D. Huntington Nicholas D. Huntington Alicia Oshlack Alicia Oshlack Sitang Gong Axel Kallies Axel Kallies Peter Vuillermin Peter Vuillermin Peter Vuillermin Peter Vuillermin Min Yang Leonard C. Harrison Leonard C. Harrison |
| author_facet | Yuxia Zhang Yuxia Zhang Yuxia Zhang Jovana Maksimovic Jovana Maksimovic Bing Huang David Peter De Souza David Peter De Souza Gaetano Naselli Gaetano Naselli Huan Chen Li Zhang Kai Weng Hanquan Liang Yanhui Xu Yanhui Xu John M. Wentworth John M. Wentworth Nicholas D. Huntington Nicholas D. Huntington Alicia Oshlack Alicia Oshlack Sitang Gong Axel Kallies Axel Kallies Peter Vuillermin Peter Vuillermin Peter Vuillermin Peter Vuillermin Min Yang Leonard C. Harrison Leonard C. Harrison |
| author_sort | Yuxia Zhang |
| collection | DOAJ |
| description | How T cells differentiate in the neonate may critically determine the ability of the infant to cope with infections, respond to vaccines and avert allergies. Previously, we found that naïve cord blood CD4+ T cells differentiated toward an IL-4-expressing phenotype when activated in the presence of TGF-β and monocyte-derived inflammatory cytokines, the latter are more highly secreted by infants who developed food allergy. Here, we show that in the absence of IL-2 or IL-12, naïve cord blood CD8+ T cells have a natural propensity to differentiate into IL-4-producing non-classic TC2 cells when they are activated alone, or in the presence of TGF-β and/or inflammatory cytokines. Mechanistically, non-classic TC2 development is associated with decreased expression of IL-2 receptor alpha (CD25) and glycolysis, and increased fatty acid metabolism and caspase-dependent cell death. Consequently, the short chain fatty acid, sodium propionate (NaPo), enhanced IL-4 expression, but exogenous IL-2 or pan-caspase inhibition prevented IL-4 expression. In children with endoscopically and histologically confirmed non-inflammatory bowel disease and non-infectious pediatric idiopathic colitis, the presence of TGF-β, NaPo, and IL-1β or TNF-α promoted TC2 differentiation in vitro. In vivo, colonic mucosa of children with colitis had significantly increased expression of IL-4 in CD8+ T cells compared with controls. In addition, activated caspase-3 and IL-4 were co-expressed in CD8+ T cells in the colonic mucosa of children with colitis. Thus, in the context of colonic inflammation and limited IL-2 signaling, CD8+ T cells differentiate into non-classic TC2 that may contribute to the pathology of inflammatory/allergic diseases in children. |
| first_indexed | 2024-04-14T06:24:08Z |
| format | Article |
| id | doaj.art-2c8ac99118e849daa9ee1ba110902e48 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-14T06:24:08Z |
| publishDate | 2018-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-2c8ac99118e849daa9ee1ba110902e482022-12-22T02:07:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-04-01910.3389/fimmu.2018.00879358166Cord Blood CD8+ T Cells Have a Natural Propensity to Express IL-4 in a Fatty Acid Metabolism and Caspase Activation-Dependent MannerYuxia Zhang0Yuxia Zhang1Yuxia Zhang2Jovana Maksimovic3Jovana Maksimovic4Bing Huang5David Peter De Souza6David Peter De Souza7Gaetano Naselli8Gaetano Naselli9Huan Chen10Li Zhang11Kai Weng12Hanquan Liang13Yanhui Xu14Yanhui Xu15John M. Wentworth16John M. Wentworth17Nicholas D. Huntington18Nicholas D. Huntington19Alicia Oshlack20Alicia Oshlack21Sitang Gong22Axel Kallies23Axel Kallies24Peter Vuillermin25Peter Vuillermin26Peter Vuillermin27Peter Vuillermin28Min Yang29Leonard C. Harrison30Leonard C. Harrison31Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, ChinaWalter and Eliza Hall Institute of Medical Research, Parkville, VIC, AustraliaDepartment of Medical Biology, University of Melbourne, Parkville, VIC, AustraliaMurdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC, AustraliaDepartment of Pediatrics, University of Melbourne, Parkville, VIC, AustraliaGuangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, ChinaDepartment of Medical Biology, University of Melbourne, Parkville, VIC, AustraliaBio21 Institute, University of Melbourne, Parkville, VIC, AustraliaWalter and Eliza Hall Institute of Medical Research, Parkville, VIC, AustraliaDepartment of Medical Biology, University of Melbourne, Parkville, VIC, AustraliaGuangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, ChinaGuangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, ChinaGuangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, ChinaSchool of Data and Computer Science, Sun Yat-sen University, Guangzhou, ChinaWalter and Eliza Hall Institute of Medical Research, Parkville, VIC, AustraliaDepartment of Medical Biology, University of Melbourne, Parkville, VIC, AustraliaWalter and Eliza Hall Institute of Medical Research, Parkville, VIC, AustraliaDepartment of Medical Biology, University of Melbourne, Parkville, VIC, AustraliaWalter and Eliza Hall Institute of Medical Research, Parkville, VIC, AustraliaDepartment of Medical Biology, University of Melbourne, Parkville, VIC, AustraliaMurdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC, AustraliaDepartment of Pediatrics, University of Melbourne, Parkville, VIC, AustraliaGuangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, ChinaWalter and Eliza Hall Institute of Medical Research, Parkville, VIC, AustraliaDepartment of Medical Biology, University of Melbourne, Parkville, VIC, AustraliaMurdoch Children’s Research Institute, Royal Children’s Hospital, Parkville, VIC, AustraliaDepartment of Pediatrics, University of Melbourne, Parkville, VIC, AustraliaBarwon Health, Geelong, VIC, AustraliaDeakin University, Geelong, VIC, AustraliaGuangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, ChinaWalter and Eliza Hall Institute of Medical Research, Parkville, VIC, AustraliaDepartment of Medical Biology, University of Melbourne, Parkville, VIC, AustraliaHow T cells differentiate in the neonate may critically determine the ability of the infant to cope with infections, respond to vaccines and avert allergies. Previously, we found that naïve cord blood CD4+ T cells differentiated toward an IL-4-expressing phenotype when activated in the presence of TGF-β and monocyte-derived inflammatory cytokines, the latter are more highly secreted by infants who developed food allergy. Here, we show that in the absence of IL-2 or IL-12, naïve cord blood CD8+ T cells have a natural propensity to differentiate into IL-4-producing non-classic TC2 cells when they are activated alone, or in the presence of TGF-β and/or inflammatory cytokines. Mechanistically, non-classic TC2 development is associated with decreased expression of IL-2 receptor alpha (CD25) and glycolysis, and increased fatty acid metabolism and caspase-dependent cell death. Consequently, the short chain fatty acid, sodium propionate (NaPo), enhanced IL-4 expression, but exogenous IL-2 or pan-caspase inhibition prevented IL-4 expression. In children with endoscopically and histologically confirmed non-inflammatory bowel disease and non-infectious pediatric idiopathic colitis, the presence of TGF-β, NaPo, and IL-1β or TNF-α promoted TC2 differentiation in vitro. In vivo, colonic mucosa of children with colitis had significantly increased expression of IL-4 in CD8+ T cells compared with controls. In addition, activated caspase-3 and IL-4 were co-expressed in CD8+ T cells in the colonic mucosa of children with colitis. Thus, in the context of colonic inflammation and limited IL-2 signaling, CD8+ T cells differentiate into non-classic TC2 that may contribute to the pathology of inflammatory/allergic diseases in children.http://journal.frontiersin.org/article/10.3389/fimmu.2018.00879/fullCD8+ T cellglycolysisfatty acid oxidationcaspasesIL-4 |
| spellingShingle | Yuxia Zhang Yuxia Zhang Yuxia Zhang Jovana Maksimovic Jovana Maksimovic Bing Huang David Peter De Souza David Peter De Souza Gaetano Naselli Gaetano Naselli Huan Chen Li Zhang Kai Weng Hanquan Liang Yanhui Xu Yanhui Xu John M. Wentworth John M. Wentworth Nicholas D. Huntington Nicholas D. Huntington Alicia Oshlack Alicia Oshlack Sitang Gong Axel Kallies Axel Kallies Peter Vuillermin Peter Vuillermin Peter Vuillermin Peter Vuillermin Min Yang Leonard C. Harrison Leonard C. Harrison Cord Blood CD8+ T Cells Have a Natural Propensity to Express IL-4 in a Fatty Acid Metabolism and Caspase Activation-Dependent Manner Frontiers in Immunology CD8+ T cell glycolysis fatty acid oxidation caspases IL-4 |
| title | Cord Blood CD8+ T Cells Have a Natural Propensity to Express IL-4 in a Fatty Acid Metabolism and Caspase Activation-Dependent Manner |
| title_full | Cord Blood CD8+ T Cells Have a Natural Propensity to Express IL-4 in a Fatty Acid Metabolism and Caspase Activation-Dependent Manner |
| title_fullStr | Cord Blood CD8+ T Cells Have a Natural Propensity to Express IL-4 in a Fatty Acid Metabolism and Caspase Activation-Dependent Manner |
| title_full_unstemmed | Cord Blood CD8+ T Cells Have a Natural Propensity to Express IL-4 in a Fatty Acid Metabolism and Caspase Activation-Dependent Manner |
| title_short | Cord Blood CD8+ T Cells Have a Natural Propensity to Express IL-4 in a Fatty Acid Metabolism and Caspase Activation-Dependent Manner |
| title_sort | cord blood cd8 t cells have a natural propensity to express il 4 in a fatty acid metabolism and caspase activation dependent manner |
| topic | CD8+ T cell glycolysis fatty acid oxidation caspases IL-4 |
| url | http://journal.frontiersin.org/article/10.3389/fimmu.2018.00879/full |
| work_keys_str_mv | AT yuxiazhang cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT yuxiazhang cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT yuxiazhang cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT jovanamaksimovic cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT jovanamaksimovic cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT binghuang cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT davidpeterdesouza cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT davidpeterdesouza cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT gaetanonaselli cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT gaetanonaselli cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT huanchen cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT lizhang cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT kaiweng cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT hanquanliang cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT yanhuixu cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT yanhuixu cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT johnmwentworth cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT johnmwentworth cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT nicholasdhuntington cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT nicholasdhuntington cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT aliciaoshlack cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT aliciaoshlack cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT sitanggong cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT axelkallies cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT axelkallies cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT petervuillermin cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT petervuillermin cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT petervuillermin cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT petervuillermin cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT minyang cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT leonardcharrison cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner AT leonardcharrison cordbloodcd8tcellshaveanaturalpropensitytoexpressil4inafattyacidmetabolismandcaspaseactivationdependentmanner |