Hrdinka Matous, Sudan Kritika, Just Sissy, Drobek Ales, Stepanek Ondrej, Schlüter Dirk, Reinhold Dirk, Jordan Bryen A, Gintschel Patricia, Schraven Burkhart, Kreutz Michael R
RG Neuroplasticity, Leibniz-Institute for Neurobiology, Magdeburg, Germany.
Institute of Molecular and Clinical Immunology, Otto-von-Guericke University, Magdeburg, Germany.
PLoS One. 2016 Sep 22;11(9):e0162863. doi: 10.1371/journal.pone.0162863. eCollection 2016.
Transmembrane adaptor proteins (TRAPs) are important organisers for the transduction of immunoreceptor-mediated signals. Prr7 is a TRAP that regulates T cell receptor (TCR) signalling and potently induces cell death when overexpressed in human Jurkat T cells. Whether endogenous Prr7 has a similar functional role is currently unknown. To address this issue, we analysed the development and function of the immune system in Prr7 knockout mice. We found that loss of Prr7 partially impairs development of single positive CD4+ T cells in the thymus but has no effect on the development of other T cell subpopulations, B cells, NK cells, or NKT cells. Moreover, Prr7 does not affect the TCR signalling pathway as T cells derived from Prr7 knockout and wild-type animals and stimulated in vitro express the same levels of the activation marker CD69, and retain their ability to proliferate and activate induced cell death programs. Importantly, Prr7 knockout mice retained the capacity to mount a protective immune response when challenged with Listeria monocytogenes infection in vivo. In addition, T cell effector functions (activation, migration, and reactivation) were normal following induction of experimental autoimmune encephalomyelitis (EAE) in Prr7 knockout mice. Collectively, our work shows that loss of Prr7 does not result in a major immune system phenotype and suggests that Prr7 has a dispensable function for TCR signalling.
跨膜衔接蛋白（TRAPs）是免疫受体介导信号转导的重要组织者。Prr7是一种TRAP，它调节T细胞受体（TCR）信号传导，并且在人Jurkat T细胞中过表达时能有效诱导细胞死亡。内源性Prr7是否具有类似的功能作用目前尚不清楚。为了解决这个问题，我们分析了Prr7基因敲除小鼠免疫系统的发育和功能。我们发现，Prr7的缺失部分损害了胸腺中单阳性CD4+ T细胞的发育，但对其他T细胞亚群、B细胞、NK细胞或NKT细胞的发育没有影响。此外，Prr7不影响TCR信号通路，因为来自Prr7基因敲除和野生型动物的T细胞在体外受到刺激时表达相同水平的激活标志物CD69，并保留其增殖和激活诱导细胞死亡程序的能力。重要的是，Prr7基因敲除小鼠在体内受到单核细胞增生李斯特菌感染时仍保留产生保护性免疫反应的能力。此外，在Prr7基因敲除小鼠中诱导实验性自身免疫性脑脊髓炎（EAE）后，T细胞效应功能（激活、迁移和再激活）正常。总的来说，我们的工作表明Prr7的缺失不会导致主要的免疫系统表型，并表明Prr7对TCR信号传导具有非必需功能。
