title: A short receptor downregulates JAK/STAT signalling to control the Drosophila cellular immune response.
abstract: 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.
authors.affiliation: Université Toulouse 3, Toulouse, France.
authors.forename: Rami
authors.initials: R
authors.lastname: Makki
authors.forename: Marie
authors.initials: M
authors.lastname: Meister
authors.forename: Delphine
authors.initials: D
authors.lastname: Pennetier
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Ubeda
authors.forename: Anne
authors.initials: A
authors.lastname: Braun
authors.forename: Virginie
authors.initials: V
authors.lastname: Daburon
authors.forename: Joanna
authors.initials: J
authors.lastname: Krzemień
authors.forename: Henri-Marc
authors.initials: HM
authors.lastname: Bourbon
authors.forename: Rui
authors.initials: R
authors.lastname: Zhou
authors.forename: Alain
authors.initials: A
authors.lastname: Vincent
authors.forename: Michèle
authors.initials: M
authors.lastname: Crozatier
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006434:Hemocytes / Q000276:immunology* / Q000378:metabolism; D006706:Homeostasis; D007111:Immunity, Cellular; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism*; D050791:STAT Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D014863:Wasps / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C120221:Orc3 protein, Drosophila; D050791:STAT Transcription Factors; D053612:Janus Kinases