Cutting edge: IL-21 is not essential for Th17 differentiation or experimental autoimmune encephalomyelitis.
Recent studies have suggested that IL-21 is a key factor in the development of IL-17-producing CD4 T cells (Th17) and that the induction of experimental autoimmune encephalomyelitis, which depends on mounting an efficient Th17 response, is reportedly impaired in the absence of IL-21 signaling. In this study, we provide supportive in vitro evidence that IL-21 can drive Th17 responses in conjunction with TGF-beta. However, more importantly we also demonstrate, using IL-21- and IL-21R-deficient mice, that IL-21 is not essential for the differentiation of Th17 cells in vitro and in vivo. Moreover, we show that IL-21- and IL-21R-deficient mice are highly susceptible to experimental autoimmune encephalomyelitis with disease scores that were comparable, or even higher at the peak of disease, to those of control mice. Thus, our results challenge the notion that IL-21 is a key factor in driving Th17 immunity and disease.
Coquet
Jonathan M
JM
Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia.
Chakravarti
Sumone
S
Smyth
Mark J
MJ
Godfrey
Dale I
DI
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D002454:Cell Differentiation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053655:Receptors, Interleukin-21 / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism; D000098546:Interleukin-21
D020381:Interleukin-17; D007378:Interleukins; D053655:Receptors, Interleukin-21; D016212:Transforming Growth Factor beta; D000098546:Interleukin-21