IL-33 Induces IL-9 Production in Human CD4+ T Cells and Basophils

IL-33, an IL-1 family member and ligand for the IL-1 receptor-related protein ST2, has been associated with induction of Th2 cytokines such as IL-4, IL-5, and IL-13. Here, we report that IL-33 can initiate IL-9 protein secretion in vitro in human CD4+ T cells and basophils isolated from peripheral blood. TGF-β has been described as a critical factor for IL-9 induction in Th2 cells; however, we found that TGF-β also induces co-production of IL-9 in purified, naïve (>99%) CD4+CD45RA+CD45RO−CD25− T cells differentiated towards a Th1 profile. Subsequently, it was demonstrated that TGF-β is important, although not an absolute requirement, for IL-9 production in CD4+ T cells. IL-9 production by purified (>95%) human basophils, cultured for 24 h with IL-3 or IL-33, was found, with a strong synergy between the two, likely to be explained by the IL-3 upregulated ST2 expression. Collectively, these data indicate that barrier functioning cells are important for the regulation of IL-9 production by immune cells in inflamed tissue

IgE-mediated basophil tumour necrosis factor alpha induces matrix metalloproteinase-9 from monocytes.

BACKGROUND. IgE-mediated activation of mast cells has been reported to induce the release of tumour necrosis alpha (TNF-?), which may display autocrine effects on these cells by inducing the generation of the tissue remodelling protease matrix metalloproteinase-9 (MMP-9). While mast cells and basophils have been shown to express complementary and partially overlapping roles, it is not clear whether a similar IgE/TNF-?/MMP-9 axis exists in the human basophil. The purpose of this study was thus to investigate whether IgE-mediated activation of human basophils induces TNF-? and MMP-9 release. METHODS. Human peripheral blood mononuclear cells (PBMC), isolated basophils and monocytes were stimulated up to 21 h with anti-IgE. Mediator releases were assessed by ELISA, and surface expressions of mediators were detected by flow cytometry. Upregulation of cytokine production was detected by Western blot and polymerase chain reaction (PCR). RESULTS. IgE-mediated activation of basophils induced the synthesis and release of both TNF-? and MMP-9 from PBMC. In contrast, IgE-mediated activation of purified basophils induced the release and cellular expression of TNF-? but not MMP-9. Isolated monocytes did not release MMP-9 upon anti-IgE stimulation, but MMP-9 release was induced by stimulating monocytes with supernatants from activated basophils, and this release was inhibited by anti-TNF-? neutralizing antibodies. CONCLUSION. Our results strongly indicate that human basophils release TNF-? following IgE-dependent activation and that this cytokine subsequently stimulates MMP-9 release from monocytes. These findings support a direct involvement of basophils in inflammation as well as suggesting a role for the basophil in tissue remodelling

A guiding map for inflammation

D.L.K. was supported by the Intramural Research Program of the National Human Genome Research Institute (NHGRI) at the US National Institutes of Health. M.G.N. was supported by an ERC Consolidator Grant (no. 310372), a Spinoza Grant from the Netherlands Organization for Scientific Research and a Competitiveness Operational Programme Grant from the Romanian Ministry of European Funds (FUSE). K.L.N. was supported by American Heart Association postdoctoral fellowship award 12POST11920023. F.C. was supported by NIH grants DK042191, DK055812, DK091222 and DK097948. F.B. was supported by an ERC Advanced Grant (ERC322566) and a Cancer Research UK Programme Grant (A16354). C.A.D. was supported by NIH grant AI15614. L.A.J. was supported by a Competitiveness Operational Programme grant from the Romanian Ministry of European Funds (HINT, ID P_37_762; MySMIS 103587) and a Dutch Arthritis Foundation grant (NR- 12-2-303). K.H.G.M. was supported by grants from Science Foundation Ireland. P.L. was supported by the RRM Charitable Fund and The National Heart, Lung, and Blood Institute (R01 HL080472). B.S. was supported by the German Research Foundation SPP1656, 749/7-1, 749/10-1, the German Cancer Foundation, the German Israel Foundation and the Horizon 2020 program. D.A.S. was supported by NIH grant R01-HL097163. A.M. was supported by ERC, AIRC and Fondazione Cariplo