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Catalpol Reactivates IL-7R–STAT5 Signaling and Reverses Radiation-Induced T Helper 1 Cells Deficiency to Limit Melanoma Metastasis to Lung
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DOI：10.1177/15347354261453338.png)
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Abstract
En 中文
<jats:sec>
<jats:title>Background:</jats:title>
<jats:p>Radiation-induced quantitative deficiency of T helper 1 (Th1) cells accelerates lung tumor development. Here, we evaluated IL-7R–STAT5 signaling in Th1 recovery after irradiation and examined how catalpol contributes to Th1 reconstitution by targeting this signaling axis in mice.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Methods:</jats:title>
<jats:p>
The recovery characteristics of irradiated Th1 cells, compared with other IFN-γ-producing (IFN-γ
<jats:sup>+</jats:sup>
) cells, were analyzed in local radiotherapy (LRT) mice challenged with lung melanoma and single low-dose total body irradiation (SLTBI) mice without tumor. IL-7R–STAT5 signaling of Th1 from LRT mice, treated with or without catalpol, was evaluated using flow cytometry and RT-qPCR. The role of IL-7–IL-7R–STAT5 signaling in irradiated Th1 cells was further confirmed in irradiated EL4 cells following administration of IL-7 or catalpol.
</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results:</jats:title>
<jats:p>
Th1 subsets showed delayed recovery in both LRT and SLTBI mice compared with other IFN-γ
<jats:sup>+</jats:sup>
cells, and irradiated Th1 cells exhibited decreased activation of IL-7R–STAT5 signaling. Quantitative reduction of Th1 cells increased lung metastasis of B16 melanoma in irradiated mice. Irradiated EL4 cells also displayed decreased IL-7R–STAT5 signaling and reduced IFN-γ production in vitro. Treatment with catalpol could restore IL-7R–STAT5 signaling and promote Th1 recovery following irradiation both in vivo and in vitro. Catalpol-mediated restoration of IL-7R–STAT5 signaling in Th1 provided superior protection against B16 melanoma metastasis to the lung.
</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusions:</jats:title>
<jats:p>IL-7R–STAT5 signaling is required for Th1 recovery after irradiation. Catalpol effectively promotes Th1 cell reconstitution and decreases B16 melanoma metastasis to the lung by enhancing IL-7R–STAT5 signaling. These findings provide new strategies for improving radiotherapy and immunotherapy outcomes in cancer.</jats:p>
</jats:sec>
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