The transcription factor lymphoid enhancer factor 1 controls invariant natural killer T cell expansion and Th2-type effector differentiation

T Carr, V Krishnamoorthy, S Yu, HH Xue… - Journal of Experimental …, 2015 - rupress.org
T Carr, V Krishnamoorthy, S Yu, HH Xue, BL Kee, M Verykokakis
Journal of Experimental Medicine, 2015rupress.org
Invariant natural killer T cells (iNKT cells) are innate-like T cells that rapidly produce
cytokines that impact antimicrobial immune responses, asthma, and autoimmunity. These
cells acquire multiple effector fates during their thymic development that parallel those of
CD4+ T helper cells. The number of Th2-type effector iNKT cells is variable in different
strains of mice, and their number impacts CD8 T, dendritic, and B cell function. Here we
demonstrate a unique function for the transcription factor lymphoid enhancer factor 1 (LEF1) …
Invariant natural killer T cells (iNKT cells) are innate-like T cells that rapidly produce cytokines that impact antimicrobial immune responses, asthma, and autoimmunity. These cells acquire multiple effector fates during their thymic development that parallel those of CD4+ T helper cells. The number of Th2-type effector iNKT cells is variable in different strains of mice, and their number impacts CD8 T, dendritic, and B cell function. Here we demonstrate a unique function for the transcription factor lymphoid enhancer factor 1 (LEF1) in the postselection expansion of iNKT cells through a direct induction of the CD127 component of the receptor for interleukin-7 (IL-7) and the transcription factor c-myc. LEF1 also directly augments expression of the effector fate–specifying transcription factor GATA3, thus promoting the development of Th2-like effector iNKT cells that produce IL-4, including those that also produce interferon-γ. Our data reveal LEF1 as a central regulator of iNKT cell number and Th2-type effector differentiation.
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