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Conserved IL-2Rγc signaling mediates lymphopoiesis in Zebrafish

Sertori, Robert, Liongue, Clifford, Basheer, Faiza, Lewis, Kanako L., Rasighaemi, Parisa, de Coninck, Dennis, Traver, David and Ward, Alister C. 2016, Conserved IL-2Rγc signaling mediates lymphopoiesis in Zebrafish, Journal of immunology, vol. 196, no. 1, pp. 135-143, doi: 10.4049/jimmunol.1403060.

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Title Conserved IL-2Rγc signaling mediates lymphopoiesis in Zebrafish
Author(s) Sertori, Robert
Liongue, Clifford
Basheer, Faiza
Lewis, Kanako L.
Rasighaemi, Parisa
de Coninck, Dennis
Traver, David
Ward, Alister C.ORCID iD for Ward, Alister C. orcid.org/0000-0001-7945-7975
Journal name Journal of immunology
Volume number 196
Issue number 1
Start page 135
End page 143
Total pages 9
Publisher American Association of Immunologists
Place of publication Bethesada, Md.
Publication date 2016-01-01
ISSN 1550-6606
Summary 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.
Language eng
DOI 10.4049/jimmunol.1403060
Field of Research 110704 Cellular Immunology
Socio Economic Objective 920103 Cardiovascular System and Diseases
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2016, American Association of Immunologists
Persistent URL http://hdl.handle.net/10536/DRO/DU:30080449

Document type: Journal Article
Collection: Molecular and Medical Research
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