Fig. 5

SHP2 and STING mediated CD4/MHC II crosstalk to TLR signaling. BMDM cells were incubated with (a–b, d–e) 100 ng/mL LPS or (c) 5 ng/mL TNF in the presence or absence of 25 nM sCD4 for the indicated time. a–d Western blotting of the indicated proteins. e Reciprocal co-immunoprecipitation between SHP2 and TRAF6 in pm cells. f TNF/IL-6 in supernatants were measured as in Fig. 3B except for that SHP2^−/− BMDM used. g Western blots as in panels (a–b) except that SHP2^−/− BMDM were used. SHP2^fl/fl macrophages were used as controls. h Survival rates and (i) serum TNF/IL-6 were measured at the indicated time after i.p. LPS in macrophage specific SHP2^−/− mice that received sCD4 (10 mg/kg). j Survival rates and (k) serum TNF/IL-6 levels 12 h post LPS injection of STING^−/− mice. l TNF/IL-6 in supernatants 4 h after LPS treatment of BMDM isolated from STING^−/− or wt mice in the absence or presence of sCD4 (25 nM). Mean ± SD are shown; n = 3–6 mice used where indicated; Statistics (ns, P > 0.05; *P < 0.05): Unpaired t test (f, i, k, l), Log-rank (Mantel-Cox) test (h, j)