Regulated expression of miR-155 is required for iNKT cell development

Alessia Burocchi, Paola Pittoni, Esmerina Tili, Alice Rigoni, Stefan Costinean, Carlo Maria Croce, Mario Paolo Colombo

Research output: Contribution to journalArticle

Abstract

Invariant natural killer T cells (iNKT cells) are CD1d-restricted, lipid antigen-reactive T lymphocytes with immunoregulatory functions. iNKT cell development in the thymus proceeds through subsequent stages, defined by the expression of CD44 and NK1.1, and is dictated by a unique gene expression program, including microRNAs. Here, we investigated whether miR-155, a microRNA involved in differentiation of most hematopoietic cells, played any role in iNKT cell development. To this end, we assessed the expression of miR-155 along iNKT cell maturation in the thymus, and studied the effects of miR-155 on iNKT cell development using Lck-miR-155 transgenic mice, which over express miR-155 in T cell lineage under the lymphocyte-specific protein tyrosine kinase (Lck) promoter. We show that miR-155 is expressed by newly selected immature wild-type iNKT cells and turned off along iNKT cells differentiation. In transgenic mice, miR-155 over-expression resulted in a substantial block of iNKT cell maturation at Stage 2, in the thymus toward an overall reduction of peripheral iNKT cells, unlike mainstream T cells. Furthermore, the effects of miR-155 over-expression on iNKT cell differentiation were cell autonomous. Finally, we identified Ets1 and ITK transcripts as relevant targets of miR-155 in iNKT cell differentiation. Altogether, these results demonstrate that a tight control of miR-155 expression is required for the development of iNKT cells.

Original languageEnglish
Article number140
JournalFrontiers in Immunology
Volume6
Issue numberMAR
DOIs
Publication statusPublished - 2015

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Natural Killer T-Cells
Thymus Gland
Cell Differentiation
MicroRNAs
T-Lymphocytes
Transgenic Mice
Cell Lineage
Protein-Tyrosine Kinases

Keywords

  • Gene expression regulation
  • iNKT cell
  • MicroRNA
  • Thymic development
  • Transgenic

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Burocchi, A., Pittoni, P., Tili, E., Rigoni, A., Costinean, S., Croce, C. M., & Colombo, M. P. (2015). Regulated expression of miR-155 is required for iNKT cell development. Frontiers in Immunology, 6(MAR), [140]. https://doi.org/10.3389/fimmu.2015.00140

Regulated expression of miR-155 is required for iNKT cell development. / Burocchi, Alessia; Pittoni, Paola; Tili, Esmerina; Rigoni, Alice; Costinean, Stefan; Croce, Carlo Maria; Colombo, Mario Paolo.

In: Frontiers in Immunology, Vol. 6, No. MAR, 140, 2015.

Research output: Contribution to journalArticle

Burocchi, A, Pittoni, P, Tili, E, Rigoni, A, Costinean, S, Croce, CM & Colombo, MP 2015, 'Regulated expression of miR-155 is required for iNKT cell development', Frontiers in Immunology, vol. 6, no. MAR, 140. https://doi.org/10.3389/fimmu.2015.00140
Burocchi A, Pittoni P, Tili E, Rigoni A, Costinean S, Croce CM et al. Regulated expression of miR-155 is required for iNKT cell development. Frontiers in Immunology. 2015;6(MAR). 140. https://doi.org/10.3389/fimmu.2015.00140
Burocchi, Alessia ; Pittoni, Paola ; Tili, Esmerina ; Rigoni, Alice ; Costinean, Stefan ; Croce, Carlo Maria ; Colombo, Mario Paolo. / Regulated expression of miR-155 is required for iNKT cell development. In: Frontiers in Immunology. 2015 ; Vol. 6, No. MAR.
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