The atypical MAPK ERK3 controls positive selection of thymocytes

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Examination of Thymic Positive and Negative Selection by Flow Cytometry
14:29

Examination of Thymic Positive and Negative Selection by Flow Cytometry

Published on: October 8, 2012

22.9K

Julien Sirois1, Jean-François Daudelin, Salix Boulet

  • 1Maisonneuve-Rosemont Hospital Research Centre, Montreal, QC, Canada; Department of Microbiology, Infection and Immunology, University of Montreal, Montreal, QC, Canada.

Immunology
|December 19, 2014
PubMed

Insights

Extracellular signal-regulated kinase 3 (ERK3) is crucial for T-cell selection. ERK3 deficiency impairs thymic positive selection and reduces T-cell receptor signaling in thymocytes.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Signaling

Background:

  • Extracellular signal-regulated kinase 3 (ERK3) is an atypical mitogen-activated protein kinase (MAPK).
  • ERK3 expression is observed during thymocyte differentiation and induced in T cells upon T-cell receptor (TCR) activation.
  • Previous studies indicated ERK3's role in T-cell biology, but its necessity in T-cell selection was unknown.

Purpose of the Study:

  • To investigate the role of ERK3 in thymic T-cell selection.
  • To determine if ERK3 expression is required for proper positive selection of thymocytes.

Main Methods:

  • Utilized a knock-in mouse model replacing ERK3 coding sequence with a β-galactosidase reporter.
  • Analyzed ERK3 expression in double-positive (DP) thymocytes during positive selection.
  • Assessed T-cell selection in ERK3-deficient mice with polyclonal and transgenic TCR repertoires.
  • Evaluated in vitro TCR stimulation response of DP thymocytes from ERK3-deficient mice.

Main Results:

  • ERK3 is expressed by DP thymocytes undergoing positive selection.
  • ERK3-deficient mice exhibited reduced positive selection in both polyclonal and transgenic TCR models.
  • DP thymocytes from ERK3-deficient mice showed a significantly diminished response to in vitro TCR stimulation.

Conclusions:

  • ERK3 expression, induced by TCR signaling, is essential for effective thymic positive selection.
  • ERK3 plays a critical role in the signaling pathways governing T-cell development in the thymus.
Keywords:
mitogen-activated protein kinasespositive selectionthymus

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