PUBLICATION

Conserved IL-2Rγc Signaling Mediates Lymphopoiesis in Zebrafish

Authors
Sertori, R., Liongue, C., Basheer, F., Lewis, K.L., Rasighaemi, P., de Coninck, D., Traver, D., Ward, A.C.
ID
ZDB-PUB-151122-1
Date
2016
Source
Journal of immunology (Baltimore, Md. : 1950)   196(1): 135-43 (Journal)
Registered Authors
Liongue, Clifford, Rasighaemi, Parisa, Traver, David, Ward, Alister C.
Keywords
none
MeSH Terms
  • Animals
  • Disease Models, Animal
  • Lymphopoiesis/genetics
  • Lymphopoiesis/immunology*
  • Cell Line
  • Severe Combined Immunodeficiency/genetics
  • Severe Combined Immunodeficiency/immunology*
  • Signal Transduction/immunology
  • HEK293 Cells
  • STAT5 Transcription Factor/genetics
  • Receptors, Interleukin-2/genetics
  • Receptors, Interleukin-2/immunology*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/immunology*
  • Humans
  • Gene Knockdown Techniques
  • B-Lymphocytes/immunology
  • T-Lymphocytes/immunology
  • MAP Kinase Kinase 1/antagonists & inhibitors
  • Zebrafish
  • Janus Kinase 3/genetics*
  • Phosphatidylinositol 3-Kinases/antagonists & inhibitors
  • Morpholinos/genetics
(all 23)
PubMed
26590317 Full text @ J. Immunol.
Abstract
The IL-2 receptor γ common (IL-2Rγc) chain is the shared subunit of the receptors for the IL-2 family of cytokines, which mediate signaling through JAK3 and various downstream pathways to regulate lymphopoiesis. Inactivating mutations in human IL-2Rγc result in SCID, a primary immunodeficiency characterized by greatly reduced numbers of lymphocytes. This study used bioinformatics, expression analysis, gene ablation, and specific pharmacologic inhibitors to investigate the function of two putative zebrafish IL-2Rγc paralogs, il-2rγc.a and il-2rγc.b, and downstream signaling components during early lymphopoiesis. Expression of il-2rγc.a commenced at 16 h post fertilization (hpf) and rose steadily from 4-6 d postfertilization (dpf) in the developing thymus, with il-2rγc.a expression also confirmed in adult T and B lymphocytes. Transcripts of il-2rγc.b were first observed from 8 hpf, but waned from 16 hpf before reaching maximal expression at 6 dpf, but this was not evident in the thymus. Knockdown of il-2rγc.a, but not il-2rγc.b, substantially reduced embryonic lymphopoiesis without affecting other aspects of hematopoiesis. Specific targeting of zebrafish Jak3 exerted a similar effect on lymphopoiesis, whereas ablation of zebrafish Stat5.1 and pharmacologic inhibition of PI3K and MEK also produced significant but smaller effects. Ablation of il-2rγc.a was further demonstrated to lead to an absence of mature T cells, but not B cells in juvenile fish. These results indicate that conserved IL-2Rγc signaling via JAK3 plays a key role during early zebrafish lymphopoiesis, which can be potentially targeted to generate a zebrafish model of human SCID.
Genes / Markers
Figures
No images available
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Marker Marker Type Name
EGFPEFGEGFP
1 - 1 of 1
Show
Mapping
Your Input Welcome
We welcome your input and comments. Please use this form to recommend updates to the information in ZFIN. We appreciate as much detail as possible and references as appropriate. We will review your comments promptly.
Citation
Sertori, R., Liongue, C., Basheer, F., Lewis, K.L., Rasighaemi, P., de Coninck, D., Traver, D., Ward, A.C. (2016) Conserved IL-2Rγc Signaling Mediates Lymphopoiesis in Zebrafish. Journal of immunology (Baltimore, Md. : 1950). 196(1):135-43.