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The atypical MAPK ERK 3 controls positive selection of thymocytes
Author(s) -
Sirois Julien,
Daudelin JeanFrançois,
Boulet Salix,
Marquis Miriam,
Meloche Sylvain,
Labrecque Nathalie
Publication year - 2015
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12433
Subject(s) - mapk/erk pathway , thymocyte , biology , kinase , t cell receptor , microbiology and biotechnology , transgene , t cell , immunology , gene , genetics , immune system
Summary Extracellular signal‐regulated kinase 3 ( ERK 3 )is an atypical member of the mitogen‐activated protein kinase ( MAPK ) family. We have previously shown that ERK 3 is expressed during thymocyte differentiation and that its expression is induced in mature peripheral T cells following activation of ERK 1/2 by T‐cell receptor ( TCR ) signalling. Herein, we have investigated whether ERK 3 expression is required for proper T‐cell selection. Using a knock‐in mouse model in which the coding sequence of ERK 3 is replaced by the gene encoding for the β ‐galactosidase reporter, we show that ERK 3 is expressed by double‐positive ( DP ) thymocytes undergoing positive selection. In ERK 3‐deficient mice with a polyclonal TCR repertoire, we observe a decrease in positive selection. This reduction in positive selection was also observed when ERK 3‐deficient mice were backcrossed to class I‐ and class II ‐restricted TCR transgenic mice. Furthermore, the response of DP thymocytes to in vitro TCR stimulation was strongly reduced in ERK 3‐deficient mice. Together, these results show that ERK 3 expression following TCR signalling is critical for proper thymic positive selection.