PMID- 20689801
OWN - NLM
STAT- MEDLINE
DCOM- 20101213
LR  - 20211020
IS  - 1545-7885 (Electronic)
IS  - 1544-9173 (Print)
IS  - 1544-9173 (Linking)
VI  - 8
IP  - 8
DP  - 2010 Aug 3
TI  - A short receptor downregulates JAK/STAT signalling to control the Drosophila 
      cellular immune response.
PG  - e1000441
LID - 10.1371/journal.pbio.1000441 [doi]
LID - e1000441
AB  - 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.
FAU - Makki, Rami
AU  - Makki R
AD  - Universite Toulouse 3, Toulouse, France.
FAU - Meister, Marie
AU  - Meister M
FAU - Pennetier, Delphine
AU  - Pennetier D
FAU - Ubeda, Jean-Michel
AU  - Ubeda JM
FAU - Braun, Anne
AU  - Braun A
FAU - Daburon, Virginie
AU  - Daburon V
FAU - Krzemien, Joanna
AU  - Krzemien J
FAU - Bourbon, Henri-Marc
AU  - Bourbon HM
FAU - Zhou, Rui
AU  - Zhou R
FAU - Vincent, Alain
AU  - Vincent A
FAU - Crozatier, Michele
AU  - Crozatier M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100803
PL  - United States
TA  - PLoS Biol
JT  - PLoS biology
JID - 101183755
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Drosophila Proteins)
RN  - 0 (Orc3 protein, Drosophila)
RN  - 0 (STAT Transcription Factors)
RN  - EC 2.7.10.2 (Janus Kinases)
SB  - IM
MH  - Animals
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - Down-Regulation
MH  - Drosophila Proteins/genetics/*metabolism
MH  - Drosophila melanogaster/genetics/*immunology/metabolism
MH  - Hemocytes/*immunology/metabolism
MH  - Homeostasis
MH  - Immunity, Cellular
MH  - Janus Kinases/genetics/*metabolism
MH  - STAT Transcription Factors/genetics/*metabolism
MH  - *Signal Transduction
MH  - Wasps/physiology
PMC - PMC2914635
COIS- The authors have declared that no competing interests exist.
EDAT- 2010/08/07 06:00
MHDA- 2010/12/14 06:00
PMCR- 2010/08/03
CRDT- 2010/08/07 06:00
PHST- 2009/09/29 00:00 [received]
PHST- 2010/06/17 00:00 [accepted]
PHST- 2010/08/07 06:00 [entrez]
PHST- 2010/08/07 06:00 [pubmed]
PHST- 2010/12/14 06:00 [medline]
PHST- 2010/08/03 00:00 [pmc-release]
AID - 09-PLBI-RA-4204R3 [pii]
AID - 10.1371/journal.pbio.1000441 [doi]
PST - epublish
SO  - PLoS Biol. 2010 Aug 3;8(8):e1000441. doi: 10.1371/journal.pbio.1000441.