Mouse pulmonary interstitial macrophages mediate the pro-tumorigenic effects of IL-9.
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ABSTRACT:
SUBMITTER: Fu Y
PROVIDER: S-EPMC9249769 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:We demonstrate that deficiency of IL-9 signaling inhibits lung tumor growth in multiple models. In defining the IL-9-responsive cells in the lung tumor models, we found IL-9 regulates lung heterogeneity by inhibiting alveolar macrophage and promoting the expansion of both CD11c+ and CD11c- interstitial macrophage populations. Interstitial macrophages are a critical IL-9-responsive population that is required to promote lung tumor growth. Mechanistically, the IL-9/macrophage axis requires arginase1 (Arg1) to mediate tumor growth. Adoptive transfer of Arg1+ but not Arg1- lung macrophages to Il9r-/- mice dramatically increases the tumor growth. In parallel, the elevated expression of IL-9R and Arg1 in human tumor associated macrophages is correlated with poor prognosis among lung cancer patients. Moreover, targeting IL-9 signaling in lung macrophages limited lung tumor growth.
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Project description:Pulmonary interstitial macrophages are required to mediate the pro-tumorigenic effects of IL-9
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