Differential Control of iNKT Cell Effector Lineage Differentiation by the Forkhead Box Protein O1 (Foxo1) Transcription Factor
The invariant NKT (iNKT) cells recognize glycolipid antigens presented by the non-classical MHC like molecule CD1d. They represent an innate T-cell lineage with the ability to rapidly produce a variety of cytokines in response to agonist stimulation to bridge innate and adaptive immunity. In thymus,...
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doaj-6c77b92ff2c446f0851137aa71c537632020-11-25T02:17:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-11-011010.3389/fimmu.2019.02710467545Differential Control of iNKT Cell Effector Lineage Differentiation by the Forkhead Box Protein O1 (Foxo1) Transcription FactorHuishan Tao0Huishan Tao1Lei Li2Lei Li3Ying Gao4Zehua Wang5Xiao-Ping Zhong6Xiao-Ping Zhong7Xiao-Ping Zhong8Department of Pediatrics-Allergy and Immunology, Duke University Medical Center, Durham, NC, United StatesDepartment of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pediatrics-Allergy and Immunology, Duke University Medical Center, Durham, NC, United StatesDepartment of Breast and Thyroid Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Pediatrics-Allergy and Immunology, Duke University Medical Center, Durham, NC, United StatesDepartment of Immunology, Duke University Medical Center, Durham, NC, United StatesThe Hematologic Malignancies and Cellular Therapy Research Program, Duke Cancer Institute, Duke University Medical Center, Durham, NC, United StatesThe invariant NKT (iNKT) cells recognize glycolipid antigens presented by the non-classical MHC like molecule CD1d. They represent an innate T-cell lineage with the ability to rapidly produce a variety of cytokines in response to agonist stimulation to bridge innate and adaptive immunity. In thymus, most iNKT cells complete their maturation and differentiate to multiple effector lineages such as iNKT-1, iNKT-2, and iNKT-17 cells that possess the capability to produce IFNγ, IL-4, and IL-17A, respectively, and play distinct roles in immune responses and diseases. Mechanisms that control iNKT lineage fate decisions are still not well understood. Evidence has revealed critical roles of Foxo1 of the forkhead box O1 subfamily of transcription factors in the immune system. However, its role in iNKT cells has been unknown. In this report, we demonstrate that deletion of Foxo1 causes severe decreases of iNKT cell total numbers due to impairment of late but not early iNKT cell development. Deficiency of Foxo1 results in decreases of iNKT-1 but increases of iNKT-17 cells. Our data reveal that Foxo1 controls iNKT effector lineage fate decision by promoting iNKT-1 but suppressing iNKT-17 lineages.https://www.frontiersin.org/article/10.3389/fimmu.2019.02710/fullinvariant NK T cellsiNKT cellsFoxo1T-betRORγtT cell development |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Huishan Tao Huishan Tao Lei Li Lei Li Ying Gao Zehua Wang Xiao-Ping Zhong Xiao-Ping Zhong Xiao-Ping Zhong |
spellingShingle |
Huishan Tao Huishan Tao Lei Li Lei Li Ying Gao Zehua Wang Xiao-Ping Zhong Xiao-Ping Zhong Xiao-Ping Zhong Differential Control of iNKT Cell Effector Lineage Differentiation by the Forkhead Box Protein O1 (Foxo1) Transcription Factor Frontiers in Immunology invariant NK T cells iNKT cells Foxo1 T-bet RORγt T cell development |
author_facet |
Huishan Tao Huishan Tao Lei Li Lei Li Ying Gao Zehua Wang Xiao-Ping Zhong Xiao-Ping Zhong Xiao-Ping Zhong |
author_sort |
Huishan Tao |
title |
Differential Control of iNKT Cell Effector Lineage Differentiation by the Forkhead Box Protein O1 (Foxo1) Transcription Factor |
title_short |
Differential Control of iNKT Cell Effector Lineage Differentiation by the Forkhead Box Protein O1 (Foxo1) Transcription Factor |
title_full |
Differential Control of iNKT Cell Effector Lineage Differentiation by the Forkhead Box Protein O1 (Foxo1) Transcription Factor |
title_fullStr |
Differential Control of iNKT Cell Effector Lineage Differentiation by the Forkhead Box Protein O1 (Foxo1) Transcription Factor |
title_full_unstemmed |
Differential Control of iNKT Cell Effector Lineage Differentiation by the Forkhead Box Protein O1 (Foxo1) Transcription Factor |
title_sort |
differential control of inkt cell effector lineage differentiation by the forkhead box protein o1 (foxo1) transcription factor |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Immunology |
issn |
1664-3224 |
publishDate |
2019-11-01 |
description |
The invariant NKT (iNKT) cells recognize glycolipid antigens presented by the non-classical MHC like molecule CD1d. They represent an innate T-cell lineage with the ability to rapidly produce a variety of cytokines in response to agonist stimulation to bridge innate and adaptive immunity. In thymus, most iNKT cells complete their maturation and differentiate to multiple effector lineages such as iNKT-1, iNKT-2, and iNKT-17 cells that possess the capability to produce IFNγ, IL-4, and IL-17A, respectively, and play distinct roles in immune responses and diseases. Mechanisms that control iNKT lineage fate decisions are still not well understood. Evidence has revealed critical roles of Foxo1 of the forkhead box O1 subfamily of transcription factors in the immune system. However, its role in iNKT cells has been unknown. In this report, we demonstrate that deletion of Foxo1 causes severe decreases of iNKT cell total numbers due to impairment of late but not early iNKT cell development. Deficiency of Foxo1 results in decreases of iNKT-1 but increases of iNKT-17 cells. Our data reveal that Foxo1 controls iNKT effector lineage fate decision by promoting iNKT-1 but suppressing iNKT-17 lineages. |
topic |
invariant NK T cells iNKT cells Foxo1 T-bet RORγt T cell development |
url |
https://www.frontiersin.org/article/10.3389/fimmu.2019.02710/full |
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