A short receptor downregulates JAK/STAT signalling to control the Drosophila cellular immune response

Rami Makki, Marie Meister, Delphine Pennetier, Jean Michel Ubeda, Anne Braun, Virginie Daburon, Joanna Krzemień, Henri Marc Bourbon, Rui Zhou, Alain Vincent, Michéle Crozatier

Research output: Contribution to journalArticle

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 microenvironment of hematopoietic stem cells in vertebrates. We have recently shown that the PSC acts in a non-cellautonomous 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 knockout 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.

Original languageEnglish (US)
Pages (from-to)33-34
Number of pages2
JournalPLoS Biology
Volume8
Issue number8
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

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Janus
Janus Kinases
Transcription
Transducers
Cellular Immunity
cell-mediated immunity
Wasps
Protein-Tyrosine Kinases
Drosophila
tyrosine
phosphotransferases (kinases)
Down-Regulation
transcription (genetics)
parasitism
receptors
Cytokine Receptors
cytokines
lymph
Lymph
Vertebrates

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Makki, R., Meister, M., Pennetier, D., Ubeda, J. M., Braun, A., Daburon, V., ... Crozatier, M. (2010). A short receptor downregulates JAK/STAT signalling to control the Drosophila cellular immune response. PLoS Biology, 8(8), 33-34. https://doi.org/10.1371/journal.pbio.1000441

A short receptor downregulates JAK/STAT signalling to control the Drosophila cellular immune response. / Makki, Rami; Meister, Marie; Pennetier, Delphine; Ubeda, Jean Michel; Braun, Anne; Daburon, Virginie; Krzemień, Joanna; Bourbon, Henri Marc; Zhou, Rui; Vincent, Alain; Crozatier, Michéle.

In: PLoS Biology, Vol. 8, No. 8, 01.01.2010, p. 33-34.

Research output: Contribution to journalArticle

Makki, R, Meister, M, Pennetier, D, Ubeda, JM, Braun, A, Daburon, V, Krzemień, J, Bourbon, HM, Zhou, R, Vincent, A & Crozatier, M 2010, 'A short receptor downregulates JAK/STAT signalling to control the Drosophila cellular immune response', PLoS Biology, vol. 8, no. 8, pp. 33-34. https://doi.org/10.1371/journal.pbio.1000441
Makki, Rami ; Meister, Marie ; Pennetier, Delphine ; Ubeda, Jean Michel ; Braun, Anne ; Daburon, Virginie ; Krzemień, Joanna ; Bourbon, Henri Marc ; Zhou, Rui ; Vincent, Alain ; Crozatier, Michéle. / A short receptor downregulates JAK/STAT signalling to control the Drosophila cellular immune response. In: PLoS Biology. 2010 ; Vol. 8, No. 8. pp. 33-34.
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