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Original Research ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Immunol. | doi: 10.3389/fimmu.2019.02710

Differential control of iNKT cell effector lineage differentiation by the Forkhead Box Protein O1 (Foxo1) transcription factor

Huishan Tao1, Lei Li1, Ying Gao2*, Zehua Wang2 and  Xiao-Ping Zhong1*
  • 1Duke University Medical Center, United States
  • 2Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, China

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 IFNg, 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.

Keywords: Invariant NK T cells, iNKT cells, IL-17A, IFNg, T cell development,, FoxO1, T-bet, RORgamma t

Received: 23 Apr 2019; Accepted: 04 Nov 2019.

Copyright: © 2019 Tao, Li, Gao, Wang and Zhong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Ying Gao, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China, gying13@163.com
Dr. Xiao-Ping Zhong, Duke University Medical Center, Durham, 27710, North Carolina, United States, zhong001@mc.duke.edu