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Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/54416
Title: Functional Characterization of a Nonmammalian IL-21: Rainbow Trout Oncorhynchus mykiss IL-21 Upregulates the Expression of the Th Cell Signature Cytokines IFN-γ, IL-10, and IL-22
Authors: Wang, T.; Díaz-Rosales, Patricia ; Costa, M. M. ; Campbell, Scott; Snow, Michael; Collet, Bertrand; Martin, Samuel A. M.; Secombes, Christopher J.
Issue Date: 2011
Publisher: American Association of Immunologists
Citation: Journal of Immunology 186(2): 708-721 (2011)
Abstract: In mammals, IL-21 is a common γ chain cytokine produced by activated CD4+ T cells and NKT cells that acts on multiple lineages of cells. Although IL-21 has also been discovered in birds, amphibians, and fish, to date, no functional studies have been reported for any nonmammalian IL-21 molecule. We have sequenced an IL-21 gene (tIL-21) in rainbow trout, which has a six-exon/five-intron structure, is expressed in immune tissues, and is induced by bacterial and viral infection and the T cell stimulant PHA. In contrast to mammals, calcium ionophore and PMA act synergistically to induce tIL-21. Recombinant tIL-21 (rtIL-21) induced a rapid and long-lasting (4–72 h) induction of expression of IFN-γ, IL-10, and IL-22, signature cytokines for Th1-, Th2-, and Th17-type responses, respectively, in head kidney leukocytes. However, rtIL-21 had little effects on the expression of other cytokines studied. rtIL-21 maintained the expression of CD8α, CD8β, and IgM at a late stage of stimulation when their expression was significantly decreased in controls and increased the expression of the Th cell markers CD4, T-bet, and GATA3. Intraperitoneal injection of rtIL-21 confirmed the in vitro bioactivity and increased the expression of IFN-γ, IL-10, IL-21, IL-22, CD8, and IgM. Inhibition experiments revealed that the activation of JAK/STAT3, Akt1/2, and PI3K pathways were responsible for rtIL-21 action. This study helps to clarify the role of IL-21 in lower vertebrates for the first time, to our knowledge, and suggests IL-21 is a likely key regulator of T and B cell function in fish.
Description: 15 páginas, 12 figuras, 2 tablas
Publisher version (URL): http://dx.doi.org/10.4049/​jimmunol.1001203
URI: http://hdl.handle.net/10261/54416
DOI: 10.4049/​jimmunol.1001203
ISSN: 0022-1767
E-ISSN: 1550-6606
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