Effects of Immunoregulatory Cytokines (IL-2, IL-7, and IL-15) on Expression of Gfi1 and U2afll4 Genes in T Cells at Different Stages of Differentiation

Bull Exp Biol Med. 2015 Jun;159(2):236-9. doi: 10.1007/s10517-015-2931-8. Epub 2015 Jun 19.

Abstract

Opposite effects of common γ-chain cytokines (IL-2, IL-7, and IL-15) on the expression of Gfi1 and U2af1l4 genes regulating alternative splicing of Ptprc gene in T cells at different stages of differentiation were demonstrated in vitro. Generally, produced a dose-dependent activating effect on T cells, while to the effects of rIL-7 and rIL-15 on T cells at different stages of differentiation were opposite to that of rIL-2: maximum concentrations of recombinant cytokines IL-7 and IL-15 produced the most pronounced inhibitory effect on U2af1l4 and to a lesser extent on Gfi1 gene expression, thus limiting activation of resting cells. This is consistent with their biological effects on T cells. In general, common γ-chain cytokines IL-2, IL-7, and IL-15 prevent differentiation of naïve T cells in vitro and limit activation of primed T cells in the absence of antigenic stimulus, which can contribute to the formation of cytokine imbalance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alternative Splicing / drug effects*
  • Cell Differentiation / immunology*
  • Cytokines / pharmacology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Dose-Response Relationship, Drug
  • Female
  • Flow Cytometry
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology*
  • Humans
  • Immunomagnetic Separation
  • Interleukin-15 / pharmacology
  • Interleukin-2 / pharmacology
  • Interleukin-7 / pharmacology
  • Leukocyte Common Antigens / genetics
  • Male
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Ribonucleoproteins / genetics
  • Ribonucleoproteins / metabolism*
  • Splicing Factor U2AF
  • Statistics, Nonparametric
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Cytokines
  • DNA-Binding Proteins
  • GFI1 protein, human
  • Interleukin-15
  • Interleukin-2
  • Interleukin-7
  • Nuclear Proteins
  • Ribonucleoproteins
  • Splicing Factor U2AF
  • Transcription Factors
  • U2AF1L4 protein, human
  • Leukocyte Common Antigens
  • PTPRC protein, human