IL-4 together with IL-1β induces antitumor Th9 cell differentiation in the absence of TGF-β signaling
IL-9-producing CD4 + (Th9) cells are a subset of CD4 + T-helper cells that are endowed with powerful antitumor capacity. Both IL-4 and TGF-β have been reported to be indispensable for Th9 cell-priming and differentiation. Here we show, by contrast, that Th9 cell development can occur in the absence...
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Veröffentlicht in: | Nature communications 2019-03, Vol.10 (1), p.1376-1376, Article 1376 |
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Sprache: | eng |
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Zusammenfassung: | IL-9-producing CD4
+
(Th9) cells are a subset of CD4
+
T-helper cells that are endowed with powerful antitumor capacity. Both IL-4 and TGF-β have been reported to be indispensable for Th9 cell-priming and differentiation. Here we show, by contrast, that Th9 cell development can occur in the absence of TGF-β signaling. When TGF-β was replaced by IL-1β, the combination of IL-1β and IL-4 efficiently promoted IL-9-producing T cells (Th9
IL-4+IL-1β
). Th9
IL-4+ IL-1β
cells are phenotypically distinct T cells compared to classic Th9 cells (Th9
IL-4+TGF-β
) and other Th cells, and are enriched for IL-1 and NF-κB gene signatures. Inhibition of NF-κB but not TGF-β-signaling negates IL-9 production by Th9
IL-4+IL-1β
cells. Furthermore, when compared with classic Th9
IL-4+TGF-β
cells, Th9
IL-4+IL-1β
cells are less exhausted, exhibit cytotoxic T effector gene signature and tumor killing function, and exert a superior antitumor response in a mouse melanoma model. Our study thus describes an alternative pathway for Th9 cell differentiation and provides a potential avenue for antitumor therapies.
CD4
+
helper T cells producing IL-9 (Th9) have been implicated in anti-tumor immunity, with Th9 differentiation inducible in vitro via IL-4 and TGFβ treatment. Here the authors show that replacing TGFβ with IL-1β induces a distinct IL-9
+
CD4
+
population that have strong cytotoxic and anti-tumor activity in preclinical mouse models. |
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ISSN: | 2041-1723 2041-1723 |
DOI: | 10.1038/s41467-019-09401-9 |