The Transcription Factor Lymphoid Enhancer Factor 1 Controls Invariant Natural Killer T Cell Expansion and Th2-type Effector Differentiation

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2015 Apr 22

PMID 25897173

Citations 38

Authors

Tiffany Carr

Veena Krishnamoorthy

Shuyang Yu

Hai-Hui Xue

Barbara L Kee

Mihalis Verykokakis

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Characterization of Freshly Isolated Human Peripheral Blood B Cells, Monocytes, CD4+ and CD8+ T Cells, and Skin Mast Cells by Quantitative Transcriptomics.

Akula S, Alvarado-Vazquez A, Haide Mendez Enriquez E, Bal G, Franke K, Wernersson S Int J Mol Sci. 2024; 25(23).

PMID: 39684762 PMC: 11642334. DOI: 10.3390/ijms252313050.

Transcriptomic diversity of innate lymphoid cells in human lymph nodes compared to BM and spleen.

Hashemi E, McCarthy C, Rao S, Malarkannan S Commun Biol. 2024; 7(1):769.

PMID: 38918571 PMC: 11199704. DOI: 10.1038/s42003-024-06450-9.

Single-cell transcriptomics reveal different maturation stages and sublineage commitment of human thymic invariant natural killer T cells.

Maas-Bauer K, Kohler N, Stell A, Zwick M, Acharya S, Rensing-Ehl A J Leukoc Biol. 2023; 115(2):401-409.

PMID: 37742056 PMC: 10799303. DOI: 10.1093/jleuko/qiad113.

Impaired thymic iNKT cell differentiation at early precursor stage in murine haploidentical bone marrow transplantation with GvHD.

Zhao W, Wang Y, Zhang X, Hao J, Zhang K, Huang X Front Immunol. 2023; 14:1203614.

PMID: 37600815 PMC: 10438461. DOI: 10.3389/fimmu.2023.1203614.

LEF1 Drives a Central Memory Program and Supports Antitumor Activity of Natural Killer T Cells.

Ngai H, Barragan G, Tian G, Balzeau J, Zhang C, Courtney A Cancer Immunol Res. 2022; 11(2):171-183.

PMID: 36484736 PMC: 9898189. DOI: 10.1158/2326-6066.CIR-22-0333.

References

Jiang Q, Li W, Hofmeister R, Young H, Hodge D, Keller J . Distinct regions of the interleukin-7 receptor regulate different Bcl2 family members. Mol Cell Biol. 2004; 24(14):6501-13. PMC: 434255. DOI: 10.1128/MCB.24.14.6501-6513.2004. View

Benlagha K, Kyin T, Beavis A, Teyton L, Bendelac A . A thymic precursor to the NK T cell lineage. Science. 2002; 296(5567):553-5. DOI: 10.1126/science.1069017. View

Yip-Schneider M, Horie M, Broxmeyer H . Characterization of interleukin-7-induced changes in tyrosine phosphorylation and c-myc gene expression in normal human T cells. Exp Hematol. 1993; 21(13):1648-56. View

Okamura R, Sigvardsson M, Galceran J, Verbeek S, Clevers H, Grosschedl R . Redundant regulation of T cell differentiation and TCRalpha gene expression by the transcription factors LEF-1 and TCF-1. Immunity. 1998; 8(1):11-20. DOI: 10.1016/s1074-7613(00)80454-9. View

Zhang J, Salojin K, Gao J, Cameron M, Bergerot I, Delovitch T . p38 mitogen-activated protein kinase mediates signal integration of TCR/CD28 costimulation in primary murine T cells. J Immunol. 1999; 162(7):3819-29. View

Egawa T, Eberl G, Taniuchi I, Benlagha K, Geissmann F, Hennighausen L . Genetic evidence supporting selection of the Valpha14i NKT cell lineage from double-positive thymocyte precursors. Immunity. 2005; 22(6):705-16. DOI: 10.1016/j.immuni.2005.03.011. View

Benlagha K, Wei D, Veiga J, Teyton L, Bendelac A . Characterization of the early stages of thymic NKT cell development. J Exp Med. 2005; 202(4):485-92. PMC: 2212852. DOI: 10.1084/jem.20050456. View

Kim P, Pai S, Brigl M, Besra G, Gumperz J, Ho I . GATA-3 regulates the development and function of invariant NKT cells. J Immunol. 2006; 177(10):6650-9. DOI: 10.4049/jimmunol.177.10.6650. View

Lim S, Hoffmann F . Smad4 cooperates with lymphoid enhancer-binding factor 1/T cell-specific factor to increase c-myc expression in the absence of TGF-beta signaling. Proc Natl Acad Sci U S A. 2006; 103(49):18580-5. PMC: 1693705. DOI: 10.1073/pnas.0604773103. View

10.

Griewank K, Borowski C, Rietdijk S, Wang N, Julien A, Wei D . Homotypic interactions mediated by Slamf1 and Slamf6 receptors control NKT cell lineage development. Immunity. 2007; 27(5):751-62. PMC: 2170879. DOI: 10.1016/j.immuni.2007.08.020. View

11.

Coquet J, Chakravarti S, Kyparissoudis K, McNab F, Pitt L, McKenzie B . Diverse cytokine production by NKT cell subsets and identification of an IL-17-producing CD4-NK1.1- NKT cell population. Proc Natl Acad Sci U S A. 2008; 105(32):11287-92. PMC: 2516267. DOI: 10.1073/pnas.0801631105. View

12.

Kovalovsky D, Uche O, Eladad S, Hobbs R, Yi W, Alonzo E . The BTB-zinc finger transcriptional regulator PLZF controls the development of invariant natural killer T cell effector functions. Nat Immunol. 2008; 9(9):1055-64. PMC: 2662733. DOI: 10.1038/ni.1641. View

13.

Savage A, Constantinides M, Han J, Picard D, Martin E, Li B . The transcription factor PLZF directs the effector program of the NKT cell lineage. Immunity. 2008; 29(3):391-403. PMC: 2613001. DOI: 10.1016/j.immuni.2008.07.011. View

14.

Michel M, Mendes-da-Cruz D, Keller A, Lochner M, Schneider E, Dy M . Critical role of ROR-γt in a new thymic pathway leading to IL-17-producing invariant NKT cell differentiation. Proc Natl Acad Sci U S A. 2008; 105(50):19845-50. PMC: 2604995. DOI: 10.1073/pnas.0806472105. View

15.

Mycko M, Ferrero I, Wilson A, Jiang W, Bianchi T, Trumpp A . Selective requirement for c-Myc at an early stage of V(alpha)14i NKT cell development. J Immunol. 2009; 182(8):4641-8. DOI: 10.4049/jimmunol.0803394. View

16.

Dose M, Sleckman B, Han J, Bredemeyer A, Bendelac A, Gounari F . Intrathymic proliferation wave essential for Valpha14+ natural killer T cell development depends on c-Myc. Proc Natl Acad Sci U S A. 2009; 106(21):8641-6. PMC: 2689024. DOI: 10.1073/pnas.0812255106. View

17.

Yu Q, Sharma A, Oh S, Moon H, Hossain M, Salay T . T cell factor 1 initiates the T helper type 2 fate by inducing the transcription factor GATA-3 and repressing interferon-gamma. Nat Immunol. 2009; 10(9):992-9. PMC: 2824257. DOI: 10.1038/ni.1762. View

18.

Kovalovsky D, Yu Y, Dose M, Emmanouilidou A, Konstantinou T, Germar K . Beta-catenin/Tcf determines the outcome of thymic selection in response to alphabetaTCR signaling. J Immunol. 2009; 183(6):3873-84. PMC: 4695211. DOI: 10.4049/jimmunol.0901369. View

19.

Chen Q, Zhang T, Pincus S, Wu S, Ricks D, Liu D . Human CD1D gene expression is regulated by LEF-1 through distal promoter regulatory elements. J Immunol. 2010; 184(9):5047-54. DOI: 10.4049/jimmunol.0901912. View

20.

Weinreich M, Odumade O, Jameson S, Hogquist K . T cells expressing the transcription factor PLZF regulate the development of memory-like CD8+ T cells. Nat Immunol. 2010; 11(8):709-16. PMC: 3051359. DOI: 10.1038/ni.1898. View