TGF-β interactions with IL-1 family members trigger IL-4-independent IL-9 production by mouse CD4(+) T cells.
TGF-β and IL-4 were recently shown to selectively upregulate IL-9 production by naïve CD4(+) T cells. We report here that TGF-β interactions with IL-1α, IL-1β, IL-18, and IL-33 have equivalent IL-9-stimulating activities that function even in IL-4-deficient animals. This was observed after in vitro antigenic stimulation of immunized or unprimed mice and after polyclonal T-cell activation. Based on intracellular IL-9 staining, all IL-9-producing cells were CD4(+) and 80-90% had proliferated, as indicated by reduced CFSE staining. In contrast to IL-9, IL-13 and IL-17 were strongly stimulated by IL-1 and either inhibited (IL-13) or were unaffected (IL-17) by addition of TGF-β. IL-9 and IL-17 production also differed in their dependence on IL-2 and regulation by IL-1/IL-23. As IL-9 levels were much lower in Th2 and Th17 cultures, our results identify TGF-β/IL-1 and TGF-β/IL-4 as the main control points of IL-9 synthesis.
Ludwig Institute for Cancer Research, Brussels Branch, Brussels, Belgium.
Catherine
C
Uyttenhove
Frank
F
Brombacher
Jacques
J
Van Snick
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002478:Cells, Cultured; D007114:Immunization; D007375:Interleukin-1 / Q000031:analogs & derivatives / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016906:Interleukin-9 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D058408:Th1-Th2 Balance; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism*
D007375:Interleukin-1; D016906:Interleukin-9; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D010047:Ovalbumin