Fig. 6: Th2-polarized microenvironment is required for sustaining the pro-metastatic effect of LMSCs. | Nature Communications

Fig. 6: Th2-polarized microenvironment is required for sustaining the pro-metastatic effect of LMSCs.

From: Lung mesenchymal stromal cells influenced by Th2 cytokines mobilize neutrophils and facilitate metastasis by producing complement C3

Fig. 6: Th2-polarized microenvironment is required for sustaining the pro-metastatic effect of LMSCs.The alternative text for this image may have been generated using AI.

A Th2 cytokines increased the expression of C3. CD4+ T cells were induced into Th2 cells, which were then cultured in fresh medium for 12 h, to generate Th2-CM. LMSCs were treated with Th2 supernatant for 24 h and were examined for C3 expression. Med, culture medium. n = 3 individual experiments. B LMSCs failed to promote lung colonization in Stat6-deficient mice. LMSCs were co-injected intravenously with 4T1 cells and LMNs were counted on day 14. n = 7, 5, 3, 5, 5, and 5 mice. C LMSCs failed to promote metastasis in Stat6-deficient mice. 4T1 cells (4 × 105) were implanted into the mammary gland fat pad and LMSCs (1 × 105) were injected 10 days later. LMNs were counted on day 30. n = 8, 9, 6, 8, 9, and 9 mice. D Depletion of IL-4 attenuated the metastasis-promoting activity of LMSCs. After co-administration of LMSCs and 4T1 cells into BALB/c mice, anti-IL-4 (α-IL-4, 50 μg per mouse) or IgG was intraperitoneally every 2 days. LMNs were counted on day 14. n = 6, 6, 5, and 6 mice. E Adoptive transfer of CD4+ T cells from WT or T-bet-deficient mice conferred a metastasis-promoting activity of LMSCs. 4T1 cells were co-injected with or without LMSCs cells into nude mice. CD4+ T cells (4 × 106) isolated from the indicated mice were injected into nude mice on day 2. LMNs were counted on day 14. n = 5, 5, 4, 4, 5, 5, 5, and 5 mice. F Adoptive transfer of Th2 cells conferred a metastasis-promoting activity of LMSCs. 4T1 cells were co-injected with LMSCs cells into nude mice. CD4+ T cells were induced into Th1 or Th2 cells, respectively, and injected (4 × 106) on day 2. LMNs were counted on day 14. n = 4, 4, and 3 mice. G IL-4/IL-13 conferred LMSCs a pro-metastatic activity. Nude mice were co-injected with 4T1 and LMSCs (control or IL-4/IL-13-treated), and were treated with IL-4/IL-13 or PBS every 4 days. LMNs were counted on day 14. n = 5 mice each. All the data are presented as mean values ± SD. ns, not significant; p < 0.05, significant, using a one-way ANOVA with Sidak’s post test for B–G; using an unpaired, two-tailed Student’s t-test for A. Source data are provided as a Source Data file.

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