Molecular mechanism of STING-mediated inhibition of the mTORC1 pathway

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FIGURE 1 WT CD2 TG CD25 CONTROL IL-2 CD3/CD28 CD3/CD28+IL

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Molecular mechanism of STING-mediated inhibition of the mTORC1 pathway. Molecular mechanism of STING-mediated inhibition of the mTORC1 pathway. (A) Naive CD4+ T cells were stimulated with anti-CD3/CD28 Abs either with rapamycin (open column) or anti-IFNAR1 Ab (grey column) or both rapamycin and anti-IFNAR1 Ab (diagonal line column) with or without (Ctrl, closed column) cGAMP for 48 h, and cell growth was assessed by a WST-8 cell proliferation assay. (B) Naive CD4+ T cells from Irf7+/+ (closed column) or Irf7−/− (open column) mice were stimulated with anti-CD3/CD28 Abs with or without cGAMP for 48 h, and cell growth was assessed by a WST-8 cell proliferation assay. (C) Quantitative analysis of the data in Fig 5E. Data were collected from four independent experiments. (D) FACS analysis of surface expression of indicated molecules and FSC on CD4+ T cells from WT and Irf3/Irf7-DKO mice upon stimulation with anti-CD3/CD28 Abs with or without cGAMP for 24 h. (E) Naive CD4+ T cells from WT or Irf3-KO mice were stimulated with anti-CD3/CD28 Abs with or without IFN-β (1 ng/ml) or cGAMP for 48 h, and cell growth was assessed by a WST-8 cell proliferation assay. (F) Naive CD4+ T cells from WT or Irf3/Irf7-DKO mice were stimulated with anti-CD3/CD28 Abs with or without IFN-β (1 ng/ml) or cGAMP for 48 h, and cell growth was assessed by a WST-8 cell proliferation assay. (G) Western blot analysis for the mTORC1 activation pathway in CD4+ T cells from Irf3+/+ or Irf3−/− mice. (H) Western blot analysis for the ER stress pathways in CD4+ T cells stimulated with anti-CD3/CD28 Abs in the presence or absence of cGAMP. Data are the mean from duplicate (A, B, E, F) ± SD. Data are representative of two independent experiments. (A, B, D, E, F, G, H) *P < 0.05, t test (compared with WT cells treated with cGAMP). (F) *P < 0.05, t test (compared with WT cells treated with cGAMP and IFN-β). Takayuki Imanishi et al. LSA 2019;2:e201800282 © 2019 Imanishi et al.