Cutting edge: opposite effects of IL-1 and IL-2 on the regulation of IL-17+ T cell pool IL-1 subverts IL-2-mediated suppression.
In this report, we show that IL-17(+)CD4(+) and IL-17(+)CD8(+) T cells are largely found in lung and digestive mucosa compartments in normal mice. Endogenous and exogenous IL-1 dramatically contribute to IL-17(+) T cell differentiation mediated by TGFbeta and IL-6. IL-1 is capable of stimulating IL-17(+) T cell differentiation in the absence of IL-6. Furthermore, although IL-2 reduces IL-17(+) T cell differentiation, IL-1 completely disables this effect. Mechanistically, IL-1 and IL-2 play opposite roles in regulating the expression of several molecules regulating Th17 cell differentiation, including the orphan nuclear receptor ROR gamma t, the IL-1 receptor, and the IL-23 receptor. IL-1 subverts the effects of IL-2 on the expression of these gene transcripts. Altogether, our work demonstrates that IL-6 is important but not indispensable for IL-17(+) T cell differentiation and that IL-1 plays a predominant role in promoting IL-17(+) T cell induction. Thus, the IL-17(+) T cell pool may be controlled by the local cytokine profile in the microenvironment.
Kryczek
Ilona
I
Department of Surgery, University of Mechigan, Ann Arbor, MI 48109, USA.
Wei
Shuang
S
Vatan
Linhua
L
Escara-Wilke
June
J
Szeliga
Wojciech
W
Keller
Evan T
ET
Zou
Weiping
W
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology*; D006131:Growth Inhibitors / Q000037:antagonists & inhibitors* / Q000502:physiology*; D007375:Interleukin-1 / Q000378:metabolism / Q000502:physiology*; D020381:Interleukin-17 / Q000096:biosynthesis*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000502:physiology*; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000502:physiology
D006131:Growth Inhibitors; D007375:Interleukin-1; D020381:Interleukin-17; D007376:Interleukin-2; D015850:Interleukin-6; D016212:Transforming Growth Factor beta