Positive and negative regulation of the IL-27 receptor during lymphoid cell activation.
Previous reports have focused on the ability of IL-27 to promote naive T cell responses but the present study reveals that surface expression of WSX-1, the ligand-specific component of the IL-27R, is low on these cells and that highest levels are found on effector and memory CD4(+) and CD8(+) T cells. Accordingly, during infection with Toxoplasma gondii, in vivo T cell activation is associated with enhanced expression of WSX-1, and, in vitro, TCR ligation can induce expression of WSX-1 regardless of the polarizing (Th1/Th2) environment present at the time of priming. However, while these data establish that mitogenic stimulation promotes expression of WSX-1 by T cells, activation of NK cells and NKT cells prompts a reduction in WSX-1 levels during acute toxoplasmosis. Together, with the finding that IL-2 can suppress expression of WSX-1 by activated CD4(+) T cells, these studies indicate that surface levels of the IL-27R can be regulated by positive and negative signals associated with lymphoid cell activation. Additionally, since high levels of WSX-1 are evident on resting NK cells, resting NKT cells, effector T cells, regulatory T cells, and memory T cells, the current work demonstrates that IL-27 can influence multiple effector cells of innate and adaptive immunity.
Villarino
Alejandro V
AV
Department of Pathobiology, University of Pennsylvania School of Veterinary Medicine, and Wistar Institute, Philadelphia, PA 19104, USA.
Larkin
Joseph
J
Saris
Christiaan J M
CJ
Caton
Andrew J
AJ
Lucas
Sophie
S
Wong
Terence
T
de Sauvage
Frederic J
FJ
Hunter
Christopher A
CA
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D015536:Down-Regulation / Q000276:immunology*; D007156:Immunologic Memory / Q000235:genetics; D007376:Interleukin-2 / Q000494:pharmacology; D007378:Interleukins / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D018121:Receptors, Cytokine / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D018123:Receptors, Interleukin; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014124:Toxoplasmosis, Animal / Q000235:genetics / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology*
C486767:Il27 protein, mouse; C484747:Il27ra protein, mouse; D007376:Interleukin-2; D007378:Interleukins; D018121:Receptors, Cytokine; D018123:Receptors, Interleukin