AUTHOR=Tao Huishan , Li Lei , Gao Ying , Wang Zehua , Zhong Xiao-Ping 

TITLE=Differential Control of iNKT Cell Effector Lineage Differentiation by the Forkhead Box Protein O1 (Foxo1) Transcription Factor

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.02710

DOI=10.3389/fimmu.2019.02710

ISSN=1664-3224

ABSTRACT=<p>The invariant NKT (<italic>i</italic>NKT) 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 <italic>i</italic>NKT cells complete their maturation and differentiate to multiple effector lineages such as <italic>i</italic>NKT-1, <italic>i</italic>NKT-2, and <italic>i</italic>NKT-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 <italic>i</italic>NKT 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 <italic>i</italic>NKT cells has been unknown. In this report, we demonstrate that deletion of Foxo1 causes severe decreases of <italic>i</italic>NKT cell total numbers due to impairment of late but not early <italic>i</italic>NKT cell development. Deficiency of Foxo1 results in decreases of <italic>i</italic>NKT-1 but increases of <italic>i</italic>NKT-17 cells. Our data reveal that Foxo1 controls <italic>i</italic>NKT effector lineage fate decision by promoting <italic>i</italic>NKT-1 but suppressing <italic>i</italic>NKT-17 lineages.</p>