Université Toulouse 3, Toulouse, France.
PLoS Biol. 2010 Aug 3;8(8):e1000441. doi: 10.1371/journal.pbio.1000441.
The posterior signalling centre (PSC), a small group of specialised cells, controls hemocyte (blood cell) homeostasis in the Drosophila larval hematopoietic organ, the lymph gland. This role of the PSC is very reminiscent of the "niche," the micro-environment of hematopoietic stem cells in vertebrates. We have recently shown that the PSC acts in a non-cell-autonomous manner to maintain janus tyrosine kinase/signal transducers and activators of transcription (JAK/STAT) signalling in hematopoietic progenitors (prohemocytes), thereby preserving the multipotent character necessary for their differentiation into lamellocytes, a cryptic and dedicated immune cell type required to fight specific immune threats such as wasp parasitism. In this report, on the basis of a knock out generated by homologous recombination, we show that a short type I cytokine-related receptor CG14225/Latran is required for switching off JAK/STAT signalling in prohemocytes. This is a prerequisite to massive differentiation of lamellocytes upon wasp parasitisation. In vivo and cell culture assays indicate that Latran forms heteromers with Domeless, the Drosophila type I cytokine signalling receptor related to mammalian GP130, and antagonises Domeless activity in a dose-dependent manner. Our analysis further shows that a primary immune response to wasp parasitism is a strong decrease in cytokine mRNA levels in the lymph gland, followed by an increase in the latran/domeless ratio. We propose that this sequence of events culminates in the complete inhibition of residual JAK/STAT signalling by Latran. JAK/STAT activity has been associated with several human diseases including leukaemia while knock-out studies in mice point to a central role of this pathway in hematopoiesis and regulation of immune functions. The specific function of Drosophila Latran is, to our knowledge, the first in vivo example of a role for a nonsignalling receptor in controlling a dedicated immune response, and thus raises the question of whether short, nonsignalling receptors also control specific aspects of vertebrate cellular immunity.
后部信号中心（PSC）是一小群专门的细胞，控制果蝇幼虫造血器官——血腔中的血细胞稳态。PSC 的这一作用非常类似于脊椎动物造血干细胞的“龛位”，即造血干细胞的微环境。我们最近表明，PSC 通过非细胞自主的方式作用于造血祖细胞（原血细胞），以维持 Janus 酪氨酸激酶/信号转导子和转录激活子（JAK/STAT）信号，从而保持其分化为 lamellocytes 的多能性特征，lamellocytes 是一种隐蔽的、专门的免疫细胞类型，需要对抗特定的免疫威胁，如黄蜂寄生。在本报告中，基于同源重组产生的敲除，我们表明，一种短型 I 细胞因子相关受体 CG14225/Latran 是关闭原血细胞中 JAK/STAT 信号所必需的。这是黄蜂寄生时大量分化成 lamellocytes 的前提条件。体内和细胞培养实验表明，Latran 与 Domeless 形成异源二聚体，Domeless 是与哺乳动物 GP130 相关的果蝇 I 型细胞因子信号受体，并以剂量依赖的方式拮抗 Domeless 的活性。我们的分析进一步表明，对黄蜂寄生的初级免疫反应是血腔中细胞因子 mRNA 水平的强烈下降，随后 latran/domeless 比值增加。我们提出，这一系列事件最终导致 Latran 完全抑制残留的 JAK/STAT 信号。JAK/STAT 活性与包括白血病在内的几种人类疾病有关，而小鼠的敲除研究表明，该途径在造血和免疫功能调节中起着核心作用。到目前为止，果蝇 Latran 的特定功能是控制专门免疫反应的非信号受体的第一个体内实例，这就提出了一个问题，即短的非信号受体是否也控制脊椎动物细胞免疫的特定方面。
